chr4-42962919-C-T
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM1PP3
The NM_001080476.3(GRXCR1):c.412C>T(p.Arg138Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,612,274 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 Uncertain significance (★★).
Frequency
Consequence
NM_001080476.3 missense
Scores
Clinical Significance
Conservation
Publications
- autosomal recessive nonsyndromic hearing loss 25Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
- nonsyndromic genetic hearing lossInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- hearing loss, autosomal recessiveInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 151900Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000602 AC: 15AN: 249104 AF XY: 0.0000962 show subpopulations
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1460374Hom.: 0 Cov.: 32 AF XY: 0.0000372 AC XY: 27AN XY: 726544 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000263 AC: 4AN: 151900Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2AN XY: 74194 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 25 Pathogenic:1Uncertain:1
- -
- -
not provided Uncertain:2
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 138 of the GRXCR1 protein (p.Arg138Cys). This variant is present in population databases (rs267606856, gnomAD 0.05%). This missense change has been observed in individual(s) with deafness (PMID: 20137778). ClinVar contains an entry for this variant (Variation ID: 196). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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. -
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26186295, 25802247, 20137778) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at