This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
ClinVar Genomic variation as it relates to human health
NM_021922.3(FANCE):c.1333C>T (p.Pro445Ser)
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.
(9)
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.
Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(4); Likely benign(2)
Uncertain significance(1); Benign(4); Likely benign(2)
9
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_021922.3(FANCE):c.1333C>T (p.Pro445Ser)
Variation ID: 134343 Accession: VCV000134343.25
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 6p21.31 6: 35460568 (GRCh38) [ NCBI UCSC ] 6: 35428345 (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 9, 2014 Feb 14, 2024 Jan 30, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_021922.3:c.1333C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_068741.1:p.Pro445Ser missense NC_000006.12:g.35460568C>T NC_000006.11:g.35428345C>T NG_011708.1:g.13208C>T LRG_498:g.13208C>T LRG_498t1:c.1333C>T LRG_498p1:p.Pro445Ser - Protein change
- P445S
- Other names
- -
- Canonical SPDI
- NC_000006.12:35460567:C:T
-
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.
-
0.00100 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD) 0.00043
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00046
Trans-Omics for Precision Medicine (TOPMed) 0.00049
1000 Genomes Project 0.00100
1000 Genomes Project 30x 0.00109
Exome Aggregation Consortium (ExAC) 0.00115
The Genome Aggregation Database (gnomAD), exomes 0.00126
- Links
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. |
|||
| FANCE | - | - |
GRCh38 GRCh37 |
583 | 720 | |
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. |
|---|---|---|---|---|
| Benign (3) |
criteria provided, single submitter
|
Feb 26, 2021 | RCV000121017.7 | |
| Conflicting interpretations of pathogenicity (5) |
criteria provided, conflicting classifications
|
Jan 30, 2024 | RCV000229190.24 | |
| Benign (1) |
criteria provided, single submitter
|
Jan 1, 2022 | RCV003153393.2 |
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. |
|
|---|---|---|---|---|---|
|
Likely benign
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Fanconi anemia complementation group E
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000462672.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
|
|
|
Likely benign
(Aug 07, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Fanconi anemia complementation group E
Affected status: unknown
Allele origin:
germline
|
Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV001431511.1
First in ClinVar: Sep 05, 2020 Last updated: Sep 05, 2020 |
|
|
|
Uncertain significance
(Jan 20, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Fanconi anemia complementation group E
Affected status: yes
Allele origin:
unknown
|
Baylor Genetics
Study: CSER-TexasKidsCanSeq
Accession: SCV001481487.2 First in ClinVar: Feb 27, 2021 Last updated: Feb 27, 2021 |
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
|
|
|
Benign
(Feb 26, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002069826.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
|
|
|
Benign
(Jan 30, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Fanconi anemia complementation group E
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000290606.10
First in ClinVar: Jul 01, 2016 Last updated: Feb 14, 2024 |
|
|
|
Benign
(Nov 04, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Fanconi anemia complementation group E
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001367672.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2.
|
|
|
Benign
(Jan 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Ovarian cancer
Affected status: yes
Allele origin:
germline
|
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University
Accession: SCV003843448.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001549790.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The FANCE p.Pro445Ser variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP … (more)
The FANCE p.Pro445Ser variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs141551053) and ClinVar (classified as benign by Invitae and as a VUS by Illumina). The variant was also identified in control databases in 326 of 282840 chromosomes (2 homozygous) at a frequency of 0.001153 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Ashkenazi Jewish in 106 of 10370 chromosomes (freq: 0.01022), South Asian in 123 of 30616 chromosomes (freq: 0.004018), Other in 12 of 7224 chromosomes (freq: 0.001661), Latino in 19 of 35440 chromosomes (freq: 0.000536), European (non-Finnish) in 55 of 129178 chromosomes (freq: 0.000426), East Asian in 8 of 19954 chromosomes (freq: 0.000401) and African in 3 of 24968 chromosomes (freq: 0.00012), but was not observed in the European (Finnish) population. The p.Pro445 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. (less)
|
|
|
not provided
(Sep 19, 2013)
|
no classification provided
Method: reference population
|
AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
|
ITMI
Accession: SCV000085185.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
|
Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
|
Comment:
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Comment:
This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2.
Comment:
The FANCE p.Pro445Ser variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs141551053) and ClinVar (classified as benign by Invitae and as a VUS by Illumina). The variant was also identified in control databases in 326 of 282840 chromosomes (2 homozygous) at a frequency of 0.001153 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Ashkenazi Jewish in 106 of 10370 chromosomes (freq: 0.01022), South Asian in 123 of 30616 chromosomes (freq: 0.004018), Other in 12 of 7224 chromosomes (freq: 0.001661), Latino in 19 of 35440 chromosomes (freq: 0.000536), European (non-Finnish) in 55 of 129178 chromosomes (freq: 0.000426), East Asian in 8 of 19954 chromosomes (freq: 0.000401) and African in 3 of 24968 chromosomes (freq: 0.00012), but was not observed in the European (Finnish) population. The p.Pro445 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as 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 variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Comment:
This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2.
Comment:
The FANCE p.Pro445Ser variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs141551053) and ClinVar (classified as benign by Invitae and as a VUS by Illumina). The variant was also identified in control databases in 326 of 282840 chromosomes (2 homozygous) at a frequency of 0.001153 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Ashkenazi Jewish in 106 of 10370 chromosomes (freq: 0.01022), South Asian in 123 of 30616 chromosomes (freq: 0.004018), Other in 12 of 7224 chromosomes (freq: 0.001661), Latino in 19 of 35440 chromosomes (freq: 0.000536), European (non-Finnish) in 55 of 129178 chromosomes (freq: 0.000426), East Asian in 8 of 19954 chromosomes (freq: 0.000401) and African in 3 of 24968 chromosomes (freq: 0.00012), but was not observed in the European (Finnish) population. The p.Pro445 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs141551053 ...
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 Sep 29, 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.