rs267606855
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001080476.3(GRXCR1):c.229C>T(p.Gln77Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000274 in 1,461,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
GRXCR1
NM_001080476.3 stop_gained
NM_001080476.3 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 3.70
Genes affected
GRXCR1 (HGNC:31673): (glutaredoxin and cysteine rich domain containing 1) This gene is one of 60 loci associated with autosomal-recessive nonsyndromic hearing impairment. This gene encodes a protein which contains GRX-like domains; these domains play a role in the S-glutathionylation of proteins and may be involved in actin organization in hair cells. [provided by RefSeq, Sep 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 4-42893495-C-T is Pathogenic according to our data. Variant chr4-42893495-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 195.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-42893495-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRXCR1 | NM_001080476.3 | c.229C>T | p.Gln77Ter | stop_gained | 1/4 | ENST00000399770.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRXCR1 | ENST00000399770.3 | c.229C>T | p.Gln77Ter | stop_gained | 1/4 | 1 | NM_001080476.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461632Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727136
GnomAD4 exome
AF:
AC:
4
AN:
1461632
Hom.:
Cov.:
33
AF XY:
AC XY:
3
AN XY:
727136
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 25 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 12, 2010 | - - |
Pathogenic, no assertion criteria provided | research | National Institute on Deafness and Communication Disorders, National Institutes of Health | Jul 05, 2018 | - - |
Hearing loss, autosomal recessive Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at