NM_181703.4(GJA5):c.525C>G (p.Tyr175Ter) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 19, 2020
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:: RCV001337728.4

Allele description [Variation Report for NM_181703.4(GJA5):c.525C>G (p.Tyr175Ter)]

NM_181703.4(GJA5):c.525C>G (p.Tyr175Ter)

Gene:

GJA5:gap junction protein alpha 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q21.2

Genomic location:

Preferred name:

NM_181703.4(GJA5):c.525C>G (p.Tyr175Ter)

HGVS:

NC_000001.11:g.147758714G>C
NG_009369.2:g.19661C>G
NM_005266.7:c.525C>G
NM_181703.4:c.525C>GMANE SELECT
NP_005257.2:p.Tyr175Ter
NP_859054.1:p.Tyr175Ter
NC_000001.10:g.147230822G>C

Protein change:

Y175*

Links:

dbSNP: rs149441155

NCBI 1000 Genomes Browser:

rs149441155

Molecular consequence:

NM_005266.7:c.525C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_181703.4:c.525C>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Atrial standstill 1 (ATRST1)
Synonyms:: ATRIAL CARDIOMYOPATHY WITH HEART BLOCK; CARDIOMYOPATHY, FAMILIAL, WITH CONDUCTION DISTURBANCE; Atrial standstill, digenic (GJA5/SCN5A)
Identifiers:: MONDO: MONDO:0007171; MedGen: C4551959; Orphanet: 1344; OMIM: 108770

Name:: Atrial fibrillation, familial, 11 (ATFB11)
Identifiers:: MONDO: MONDO:0013544; MedGen: C3279693; OMIM: 614049

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001531340	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 19, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001531340

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 19, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001531340.4

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

Description

This variant has not been reported in the literature in individuals with GJA5-related conditions. This sequence change results in a premature translational stop signal in the GJA5 gene (p.Tyr175*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 184 amino acids of the GJA5 protein. This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Feb 28, 2024

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