4-42893497-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong
The NM_001080476.3(GRXCR1):c.231G>T(p.Gln77His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001080476.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152134Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249306Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135234
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461634Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727134
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74314
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 19, 2024 | In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 22, 2024 | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 77 of the GRXCR1 protein (p.Gln77His). This variant is present in population databases (rs368876169, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with GRXCR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 504593). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt GRXCR1 protein function with a negative predictive value of 80%. 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. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 09, 2016 | The p.Gln77His variant in GRXCR1 has not been previously reported in individuals with hearing loss. This variant has been identified in 1/4090 African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/ EVS/; dbSNP rs368876169). Although this variant has been seen in the general pop ulation, its frequency is not high enough to rule out a pathogenic role. Computa tional prediction tools and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Gln77His vari ant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at