4-42893418-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001080476.3(GRXCR1):c.152G>A(p.Gly51Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,613,698 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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Consequence
NM_001080476.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRXCR1 | NM_001080476.3 | c.152G>A | p.Gly51Glu | missense_variant | 1/4 | ENST00000399770.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRXCR1 | ENST00000399770.3 | c.152G>A | p.Gly51Glu | missense_variant | 1/4 | 1 | NM_001080476.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152058Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 249190Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135184
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461640Hom.: 0 Cov.: 33 AF XY: 0.0000303 AC XY: 22AN XY: 727130
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152058Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74266
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 13, 2014 | Variant classified as Uncertain Significance - Favor Benign. The Gly51Glu varian t in GRXCR1 has been previously reported in at least one Iranian individual with hearing loss and was also identified in Iranian control chromosomes; however, t he frequency of this variant in either cohort was not described (Odeh 2010). Th is variant has not been identified in large population studies. The glycine (Gl y) at position 51 is not conserved in evolutionarily distant species suggesting that a change at this position may be tolerated. Additional computational predi ction tools suggest that this variant may not impact the protein, though this in formation is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the Gly51Glu variant is uncertain, the conservatio n data and the identification of this variant in control chromosomes as reported in the literature suggests that it is more likely to be benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at