NM_001080476.3(GRXCR1):c.784C>T (p.Arg262Ter) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 6, 2025
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:: RCV001860247.5

Allele description [Variation Report for NM_001080476.3(GRXCR1):c.784C>T (p.Arg262Ter)]

NM_001080476.3(GRXCR1):c.784C>T (p.Arg262Ter)

Gene:

GRXCR1:glutaredoxin and cysteine rich domain containing 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p13

Genomic location:

Preferred name:

NM_001080476.3(GRXCR1):c.784C>T (p.Arg262Ter)

HGVS:

NC_000004.12:g.43030451C>T
NG_027718.1:g.142186C>T
NM_001080476.3:c.784C>TMANE SELECT
NP_001073945.1:p.Arg262Ter
NP_001073945.1:p.Arg262Ter
NC_000004.11:g.43032468C>T
NM_001080476.2:c.784C>T
p.Arg262X

Protein change:

R262*

Links:

dbSNP: rs761349153

NCBI 1000 Genomes Browser:

rs761349153

Molecular consequence:

NM_001080476.3:c.784C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002307881	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 6, 2025)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25802247, 31389194, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002307881

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 6, 2025)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Novel mutation in GRXCR1 at DFNB25 lead to progressive hearing loss and dizziness.

Mori K, Miyanohara I, Moteki H, Nishio SY, Kurono Y, Usami S.

Ann Otol Rhinol Laryngol. 2015 May;124 Suppl 1:129S-34S. doi: 10.1177/0003489415575061. Epub 2015 Mar 23.

PubMed [citation]

PMID:: 25802247

Sequence variants in genes causing nonsyndromic hearing loss in a Pakistani cohort.

Khan A, Han S, Wang R, Ansar M, Ahmad W, Zhang X.

Mol Genet Genomic Med. 2019 Sep;7(9):e917. doi: 10.1002/mgg3.917. Epub 2019 Aug 6.

PubMed [citation]

PMID:: 31389194
PMCID:: PMC6732339

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002307881.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Arg262*) in the GRXCR1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 29 amino acid(s) of the GRXCR1 protein. This variant is present in population databases (rs761349153, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with deafness (PMID: 25802247, 31389194). ClinVar contains an entry for this variant (Variation ID: 505242). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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: Dec 14, 2025

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