NM_004100.5(EYA4):c.925A>G (p.Thr309Ala) AND not specified

Germline classification:: Benign (1 submission)
Last evaluated:: Apr 26, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001420897.1

Allele description [Variation Report for NM_004100.5(EYA4):c.925A>G (p.Thr309Ala)]

NM_004100.5(EYA4):c.925A>G (p.Thr309Ala)

Gene:

EYA4:EYA transcriptional coactivator and phosphatase 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q23.2

Genomic location:

Preferred name:

NM_004100.5(EYA4):c.925A>G (p.Thr309Ala)

HGVS:

NC_000006.12:g.133468686A>G
NG_011596.2:g.232330A>G
NM_001301012.2:c.763A>G
NM_001301013.2:c.925A>G
NM_001370458.1:c.856A>G
NM_001370459.1:c.763A>G
NM_004100.5:c.925A>GMANE SELECT
NM_172103.4:c.856A>G
NM_172105.4:c.925A>G
NP_001287941.1:p.Thr255Ala
NP_001287942.1:p.Thr309Ala
NP_001357387.1:p.Thr286Ala
NP_001357388.1:p.Thr255Ala
NP_004091.3:p.Thr309Ala
NP_742101.2:p.Thr286Ala
NP_742103.1:p.Thr309Ala
LRG_418t1:c.925A>G
LRG_418:g.232330A>G
LRG_418p1:p.Thr309Ala
NC_000006.11:g.133789824A>G
NM_004100.4:c.925A>G

Protein change:

T255A

Links:

dbSNP: rs556335059

NCBI 1000 Genomes Browser:

rs556335059

Molecular consequence:

NM_001301012.2:c.763A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001301013.2:c.925A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370458.1:c.856A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370459.1:c.763A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004100.5:c.925A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172103.4:c.856A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172105.4:c.925A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001623335	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Apr 26, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001623335

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Apr 26, 2021)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001623335.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: EYA4 c.925A>G (p.Thr309Ala) results in a non-conservative amino acid change in the encoded protein sequence. Two of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00033 in 250638 control chromosomes, predominantly at a frequency of 0.0026 within the South Asian subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 166 fold of the estimated maximal expected allele frequency for a pathogenic variant in EYA4 causing Dilated Cardiomyopathy phenotype (1.6e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.925A>G in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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