X-71224537-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM1BP4_ModerateBP6BS2
The NM_000166.6(GJB1):c.830G>A(p.Ser277Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000707 in 1,188,349 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 33 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000166.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GJB1 | NM_000166.6 | c.830G>A | p.Ser277Asn | missense_variant | Exon 2 of 2 | ENST00000361726.7 | NP_000157.1 | |
GJB1 | NM_001097642.3 | c.830G>A | p.Ser277Asn | missense_variant | Exon 2 of 2 | NP_001091111.1 | ||
GJB1 | XM_011530907.3 | c.830G>A | p.Ser277Asn | missense_variant | Exon 2 of 2 | XP_011529209.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000268 AC: 3AN: 111804Hom.: 0 Cov.: 22 AF XY: 0.0000294 AC XY: 1AN XY: 33968
GnomAD3 exomes AF: 0.0000432 AC: 6AN: 138854Hom.: 0 AF XY: 0.0000690 AC XY: 3AN XY: 43466
GnomAD4 exome AF: 0.0000752 AC: 81AN: 1076545Hom.: 0 Cov.: 31 AF XY: 0.0000916 AC XY: 32AN XY: 349297
GnomAD4 genome AF: 0.0000268 AC: 3AN: 111804Hom.: 0 Cov.: 22 AF XY: 0.0000294 AC XY: 1AN XY: 33968
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The p.S277N variant (also known as c.830G>A), located in coding exon 1 of the GJB1 gene, results from a G to A substitution at nucleotide position 830. The serine at codon 277 is replaced by asparagine, an amino acid with highly similar properties. Based on data from the Genome Aggregation Database (gnomAD), the A allele has an overall frequency of approximately 0.004% (6/138854) total alleles studied, including a total of 3 hemizygotes. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. Computational tools predict that this variant is not damaging. -
Charcot-Marie-Tooth disease Benign:1
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Charcot-Marie-Tooth Neuropathy X Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at