13-20189304-A-G
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_Strong
The NM_004004.6(GJB2):āc.278T>Cā(p.Met93Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,738 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M93I) has been classified as Likely pathogenic.
Frequency
Consequence
NM_004004.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GJB2 | NM_004004.6 | c.278T>C | p.Met93Thr | missense_variant | 2/2 | ENST00000382848.5 | |
GJB2 | XM_011535049.3 | c.278T>C | p.Met93Thr | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GJB2 | ENST00000382848.5 | c.278T>C | p.Met93Thr | missense_variant | 2/2 | 1 | NM_004004.6 | P1 | |
GJB2 | ENST00000382844.2 | c.278T>C | p.Met93Thr | missense_variant | 1/1 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251230Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135792
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461738Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727184
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | May 09, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at