This sequence change creates a premature translational stop signal (p.Ser329Leufs*4) in the GPR179 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GPR179 are known to be pathogenic (PMID: 22325361, 22325362). This variant is present in population databases (rs770066665, gnomAD 0.3%), including at least one homozygous and/or hemizygous individual. This premature translational stop signal has been observed in individual(s) with congenital stationary night blindness (PMID: 22325361). ClinVar contains an entry for this variant (Variation ID: 31204). For these reasons, this variant has been classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_001004334.4(GPR179):c.984del (p.Ser329fs)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(10)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic
10
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001004334.4(GPR179):c.984del (p.Ser329fs)
Variation ID: 31204 Accession: VCV000031204.21
- Type and length
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Deletion, 1 bp
- Location
-
Cytogenetic: 17q12 17: 38337640 (GRCh38) [ NCBI UCSC ] 17: 36493523 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jun 18, 2015 Oct 13, 2024 Jul 22, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001004334.4:c.984del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001004334.3:p.Ser329fs frameshift NM_001004334.3:c.984delC NC_000017.11:g.38337643del NC_000017.10:g.36493526del NG_032655.2:g.11171del - Protein change
- S329fs
- Other names
- -
- Canonical SPDI
- NC_000017.11:38337639:GGGG:GGG
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
- Comment on variant
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| GPR179 | - | - |
GRCh38 GRCh38 GRCh37 |
1310 | 1320 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Jul 26, 2023 | RCV000024203.11 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Dec 23, 2023 | RCV000309713.11 | |
| Pathogenic (2) |
criteria provided, single submitter
|
Nov 10, 2016 | RCV000505034.6 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Feb 1, 2019 | RCV001073427.3 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jul 22, 2024 | RCV004595887.1 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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|---|---|---|---|---|---|
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Pathogenic
(Dec 23, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001592171.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Ser329Leufs*4) in the GPR179 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Ser329Leufs*4) in the GPR179 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GPR179 are known to be pathogenic (PMID: 22325361, 22325362). This variant is present in population databases (rs770066665, gnomAD 0.3%), including at least one homozygous and/or hemizygous individual. This premature translational stop signal has been observed in individual(s) with congenital stationary night blindness (PMID: 22325361). ClinVar contains an entry for this variant (Variation ID: 31204). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Nov 10, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital stationary night blindness
(Autosomal recessive inheritance)
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000967791.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
Comment:
The p.Ser329LeufsX4 variant in GPR179 has been reported three individuals with c omplete congenital stationary night blindness in the compound heterozygous state (Audo 2012, Peachey … (more)
The p.Ser329LeufsX4 variant in GPR179 has been reported three individuals with c omplete congenital stationary night blindness in the compound heterozygous state (Audo 2012, Peachey 2012). This variant has also been identified in 61/120,604 of chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs770066665). This p.Ser329LeufsX4 variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at posit ion 329 and leads to a premature termination codon 4 amino acids downstream. Thi s alteration is then predicted to lead to a truncated or absent protein. In summ ary, this variant meets criteria to be classified as pathogenic for congenital s tationary night blindness in an autosomal recessive manner based upon case obser vations, low frequency in controls, and a predicted null effect on protein funct ion. (less)
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Feb 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Retinal dystrophy
Affected status: yes
Allele origin:
germline
|
Blueprint Genetics
Accession: SCV001238968.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
|
|
|
|
Pathogenic
(Jun 17, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001762090.1
First in ClinVar: Jul 30, 2021 Last updated: Jul 30, 2021 |
Clinical Features:
Congenital stationary night blindness (present) , Retinoschisis (present)
Sex: male
|
|
|
Pathogenic
(Jun 13, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000329996.7
First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023 |
Comment:
Reported previously in the homozygous state and in the compound heterozygous state with another GPR179 variant, in association with congenital stationary night blindness (Peachey et … (more)
Reported previously in the homozygous state and in the compound heterozygous state with another GPR179 variant, in association with congenital stationary night blindness (Peachey et al., 2012; Audo et al., 2012; Carss et al., 2017); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30609409, 30487145, 22325361, 28041643, 31980526, 32581362, 31589614, 27535533, 22325362) (less)
|
|
|
Pathogenic
(Jul 22, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital Stationary Night Blindness, Recessive
Affected status: unknown
Allele origin:
unknown
|
Illumina Laboratory Services, Illumina
Accession: SCV000402523.4
First in ClinVar: Dec 06, 2016 Last updated: Aug 04, 2024 |
|
|
|
Pathogenic
(Jul 26, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital stationary night blindness 1E
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
paternal
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004027725.2
First in ClinVar: Aug 26, 2023 Last updated: Oct 13, 2024 |
Comment:
Criteria applied: PVS1,PS4_MOD,PM2_SUP
Clinical Features:
High myopia (present) , Abnormality of the kidney (present) , Asthma (present) , Retinal degeneration (present) , Retinal dystrophy (present) , Strabismus (present) , Night … (more)
High myopia (present) , Abnormality of the kidney (present) , Asthma (present) , Retinal degeneration (present) , Retinal dystrophy (present) , Strabismus (present) , Night blindness (present) (less)
Sex: female
|
|
|
Pathogenic
(May 06, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital stationary night blindness 1E
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002767357.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with autosomal recessive complete congenital stationary night blindness, type 1E (MIM#614565). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (150 heterozygotes, 1 homozygote). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Many other loss of function variants have previously been classified as pathogenic in individuals with night blindness (ClinVar, DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. The variant has previously been reported as in multiple individuals with autosomal recessive complete congenital stationary night blindness (ClinVar, PMID: 22325361, PMID: 22325362). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
|
|
|
Pathogenic
(Feb 10, 2012)
|
no assertion criteria provided
Method: literature only
|
NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 1E
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000045494.2
First in ClinVar: Apr 04, 2013 Last updated: Jun 18, 2015 |
Comment on evidence:
In 2 unrelated probands with complete congenital stationary night blindness type 1E (CSNB1E; 614565), Peachey et al. (2012) identified compound heterozygosity for a 1-bp deletion … (more)
In 2 unrelated probands with complete congenital stationary night blindness type 1E (CSNB1E; 614565), Peachey et al. (2012) identified compound heterozygosity for a 1-bp deletion (984delC) in the GPR179 gene, predicted to result in premature protein truncation, and another mutation: in the 10-year-old male proband, the second mutation was another 1-bp deletion (187delC; 614515.0006), also predicted to result in premature protein truncation, whereas in the 20-year-old female proband of Norwegian descent, the second mutation was a 659A-G transition resulting in a tyr220-to-cys (Y220C; 614515.0007) substitution. The boy's unaffected parents were each heterozygous for 1 of the mutations he carried; DNA from the parents of the other proband was unavailable. None of the 3 mutations was found in 210 control chromosomes. (less)
|
|
|
Pathogenic
(Jan 01, 2015)
|
no assertion criteria provided
Method: research
|
Congenital stationary night blindness
Affected status: yes
Allele origin:
unknown
|
NIHR Bioresource Rare Diseases, University of Cambridge
Accession: SCV000598885.1
First in ClinVar: Sep 09, 2017 Last updated: Sep 09, 2017 |
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: European
|
Comment:
Comment:
The p.Ser329LeufsX4 variant in GPR179 has been reported three individuals with c omplete congenital stationary night blindness in the compound heterozygous state (Audo 2012, Peachey 2012). This variant has also been identified in 61/120,604 of chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs770066665). This p.Ser329LeufsX4 variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at posit ion 329 and leads to a premature termination codon 4 amino acids downstream. Thi s alteration is then predicted to lead to a truncated or absent protein. In summ ary, this variant meets criteria to be classified as pathogenic for congenital s tationary night blindness in an autosomal recessive manner based upon case obser vations, low frequency in controls, and a predicted null effect on protein funct ion.
Comment:
Reported previously in the homozygous state and in the compound heterozygous state with another GPR179 variant, in association with congenital stationary night blindness (Peachey et al., 2012; Audo et al., 2012; Carss et al., 2017); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30609409, 30487145, 22325361, 28041643, 31980526, 32581362, 31589614, 27535533, 22325362)
Comment:
Criteria applied: PVS1,PS4_MOD,PM2_SUP
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with autosomal recessive complete congenital stationary night blindness, type 1E (MIM#614565). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (150 heterozygotes, 1 homozygote). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Many other loss of function variants have previously been classified as pathogenic in individuals with night blindness (ClinVar, DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. The variant has previously been reported as in multiple individuals with autosomal recessive complete congenital stationary night blindness (ClinVar, PMID: 22325361, PMID: 22325362). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
This sequence change creates a premature translational stop signal (p.Ser329Leufs*4) in the GPR179 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GPR179 are known to be pathogenic (PMID: 22325361, 22325362). This variant is present in population databases (rs770066665, gnomAD 0.3%), including at least one homozygous and/or hemizygous individual. This premature translational stop signal has been observed in individual(s) with congenital stationary night blindness (PMID: 22325361). ClinVar contains an entry for this variant (Variation ID: 31204). For these reasons, this variant has been classified as Pathogenic.
Comment:
The p.Ser329LeufsX4 variant in GPR179 has been reported three individuals with c omplete congenital stationary night blindness in the compound heterozygous state (Audo 2012, Peachey 2012). This variant has also been identified in 61/120,604 of chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs770066665). This p.Ser329LeufsX4 variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at posit ion 329 and leads to a premature termination codon 4 amino acids downstream. Thi s alteration is then predicted to lead to a truncated or absent protein. In summ ary, this variant meets criteria to be classified as pathogenic for congenital s tationary night blindness in an autosomal recessive manner based upon case obser vations, low frequency in controls, and a predicted null effect on protein funct ion.
Comment:
Reported previously in the homozygous state and in the compound heterozygous state with another GPR179 variant, in association with congenital stationary night blindness (Peachey et al., 2012; Audo et al., 2012; Carss et al., 2017); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30609409, 30487145, 22325361, 28041643, 31980526, 32581362, 31589614, 27535533, 22325362)
Comment:
Criteria applied: PVS1,PS4_MOD,PM2_SUP
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with autosomal recessive complete congenital stationary night blindness, type 1E (MIM#614565). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (150 heterozygotes, 1 homozygote). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Many other loss of function variants have previously been classified as pathogenic in individuals with night blindness (ClinVar, DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. The variant has previously been reported as in multiple individuals with autosomal recessive complete congenital stationary night blindness (ClinVar, PMID: 22325361, PMID: 22325362). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| GPR179 is required for depolarizing bipolar cell function and is mutated in autosomal-recessive complete congenital stationary night blindness. | Peachey NS | American journal of human genetics | 2012 | PMID: 22325362 |
| Whole-exome sequencing identifies mutations in GPR179 leading to autosomal-recessive complete congenital stationary night blindness. | Audo I | American journal of human genetics | 2012 | PMID: 22325361 |
Text-mined citations for rs770066665 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.
NCBI staff reviewed the sequence information reported in PubMed 22325362 Fig. 5C to determine the location of this allele on the current reference sequence.