VCV000167416.12 - ClinVar

NM_001368894.2(PAX6):c.1032G>A (p.Pro344=)

Germline

Classification

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.

(4)

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(1); Likely benign(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001368894.2(PAX6):c.1032G>A (p.Pro344=)

Variation ID: 167416 Accession: VCV000167416.12

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p13 11: 31793480 (GRCh38) [ NCBI UCSC ] 11: 31815028 (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	Apr 9, 2018	Oct 8, 2024	Dec 30, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001368894.2:c.1032G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001355823.1:p.Pro344=	synonymous
NM_000280.6:c.990G>A	NP_000271.1:p.Pro330=	synonymous
NM_001127612.3:c.990G>A	NP_001121084.1:p.Pro330=	synonymous
NM_001258462.3:c.1032G>A	NP_001245391.1:p.Pro344=	synonymous
NM_001258463.2:c.1032G>A	NP_001245392.1:p.Pro344=	synonymous
NM_001258464.2:c.990G>A	NP_001245393.1:p.Pro330=	synonymous
NM_001258465.3:c.990G>A	NP_001245394.1:p.Pro330=	synonymous
NM_001310158.2:c.1032G>A	NP_001297087.1:p.Pro344=	synonymous
NM_001310159.1:c.990G>A	NP_001297088.1:p.Pro330=	synonymous
NM_001310160.2:c.582G>A	NP_001297089.1:p.Pro194=	synonymous
NM_001310161.3:c.582G>A	NP_001297090.1:p.Pro194=	synonymous
NM_001368887.2:c.990G>A	NP_001355816.1:p.Pro330=	synonymous
NM_001368888.2:c.990G>A	NP_001355817.1:p.Pro330=	synonymous
NM_001368889.2:c.990G>A	NP_001355818.1:p.Pro330=	synonymous
NM_001368890.2:c.990G>A	NP_001355819.1:p.Pro330=	synonymous
NM_001368891.2:c.990G>A	NP_001355820.1:p.Pro330=	synonymous
NM_001368892.2:c.1032G>A	NP_001355821.1:p.Pro344=	synonymous
NM_001368893.2:c.1032G>A	NP_001355822.1:p.Pro344=	synonymous
NM_001368899.2:c.582G>A	NP_001355828.1:p.Pro194=	synonymous
NM_001368900.2:c.582G>A	NP_001355829.1:p.Pro194=	synonymous
NM_001368901.2:c.582G>A	NP_001355830.1:p.Pro194=	synonymous
NM_001368902.2:c.582G>A	NP_001355831.1:p.Pro194=	synonymous
NM_001368903.2:c.582G>A	NP_001355832.1:p.Pro194=	synonymous
NM_001368904.2:c.582G>A	NP_001355833.1:p.Pro194=	synonymous
NM_001368905.2:c.582G>A	NP_001355834.1:p.Pro194=	synonymous
NM_001368906.2:c.582G>A	NP_001355835.1:p.Pro194=	synonymous
NM_001368907.2:c.582G>A	NP_001355836.1:p.Pro194=	synonymous
NM_001368908.2:c.582G>A	NP_001355837.1:p.Pro194=	synonymous
NM_001368909.2:c.582G>A	NP_001355838.1:p.Pro194=	synonymous
NM_001368910.2:c.1233G>A	NP_001355839.1:p.Pro411=	synonymous
NM_001368911.2:c.1035G>A	NP_001355840.1:p.Pro345=	synonymous
NM_001368912.2:c.1032G>A	NP_001355841.1:p.Pro344=	synonymous
NM_001368913.2:c.1032G>A	NP_001355842.1:p.Pro344=	synonymous
NM_001368914.2:c.1032G>A	NP_001355843.1:p.Pro344=	synonymous
NM_001368915.2:c.990G>A	NP_001355844.1:p.Pro330=	synonymous
NM_001368916.2:c.990G>A	NP_001355845.1:p.Pro330=	synonymous
NM_001368917.2:c.990G>A	NP_001355846.1:p.Pro330=	synonymous
NM_001368918.2:c.1107G>A	NP_001355847.1:p.Pro369=	synonymous
NM_001368919.2:c.1107G>A	NP_001355848.1:p.Pro369=	synonymous
NM_001368920.2:c.1065G>A	NP_001355849.1:p.Pro355=	synonymous
NM_001368921.2:c.831G>A	NP_001355850.1:p.Pro277=	synonymous
NM_001368922.2:c.831G>A	NP_001355851.1:p.Pro277=	synonymous
NM_001368923.2:c.831G>A	NP_001355852.1:p.Pro277=	synonymous
NM_001368924.2:c.831G>A	NP_001355853.1:p.Pro277=	synonymous
NM_001368925.2:c.831G>A	NP_001355854.1:p.Pro277=	synonymous
NM_001368926.2:c.831G>A	NP_001355855.1:p.Pro277=	synonymous
NM_001368927.2:c.831G>A	NP_001355856.1:p.Pro277=	synonymous
NM_001368928.2:c.789G>A	NP_001355857.1:p.Pro263=	synonymous
NM_001368929.2:c.582G>A	NP_001355858.1:p.Pro194=	synonymous
NM_001368930.2:c.387G>A	NP_001355859.1:p.Pro129=	synonymous
NM_001604.5:c.1032G>A
NM_001604.6:c.1032G>A	NP_001595.2:p.Pro344=	synonymous
NR_160916.2:n.1371G>A		non-coding transcript variant
NR_160917.2:n.1376G>A		non-coding transcript variant
NC_000011.10:g.31793480C>T
NC_000011.9:g.31815028C>T
NG_008679.1:g.29482G>A
LRG_720:g.29482G>A
LRG_720t1:c.990G>A

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000011.10:31793479:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

0.00020 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

Exome Aggregation Consortium (ExAC) 0.00012

The Genome Aggregation Database (gnomAD), exomes 0.00012

1000 Genomes Project 0.00020

1000 Genomes Project 30x 0.00031

Trans-Omics for Precision Medicine (TOPMed) 0.00041

The Genome Aggregation Database (gnomAD) 0.00048

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00062

Links

ClinGen: CA234479 dbSNP: rs146261351 VarSome

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
Gene	OMIM	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.
PAX6		Sufficient evidence for dosage pathogenicity	Little evidence for dosage pathogenicity	GRCh38 GRCh37	695	899

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.
not specified	Likely benign (1)	criteria provided, single submitter	Feb 9, 2017	RCV000153640.5
not provided	Uncertain significance (1)	criteria provided, single submitter	Feb 27, 2014	RCV000723685.4
Aniridia 1 Irido-corneo-trabecular dysgenesis	Benign (1)	criteria provided, single submitter	Dec 30, 2023	RCV001518660.7
PAX6-related disorder	Likely benign (1)	no assertion criteria provided	Jun 18, 2019	RCV004532730.2

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.
Uncertain significance (Feb 27, 2014)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000203190.7 First in ClinVar: Feb 02, 2015 Last updated: Dec 15, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PAX6 Number of individuals with the variant: 1 Sex: mixed
Likely benign (Feb 09, 2017)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000715965.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Benign (Dec 30, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Aniridia 1 Irido-corneo-trabecular dysgenesis Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001727400.4 First in ClinVar: Jun 15, 2021 Last updated: Feb 28, 2024
Likely benign (Jun 18, 2019)	no assertion criteria provided Method: clinical testing	PAX6-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004719795.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PAX6	-	-	-	-

Text-mined citations for rs146261351 ...

These 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

ClinVar Genomic variation as it relates to human health

NM_001368894.2(PAX6):c.1032G>A (p.Pro344=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs146261351 ...