6-121446894-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP2
The NM_000165.5(GJA1):āc.47C>Gā(p.Ala16Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,508 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_000165.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GJA1 | NM_000165.5 | c.47C>G | p.Ala16Gly | missense_variant | Exon 2 of 2 | ENST00000282561.4 | NP_000156.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GJA1 | ENST00000282561.4 | c.47C>G | p.Ala16Gly | missense_variant | Exon 2 of 2 | 1 | NM_000165.5 | ENSP00000282561.3 | ||
GJA1 | ENST00000647564.1 | c.47C>G | p.Ala16Gly | missense_variant | Exon 2 of 2 | ENSP00000497565.1 | ||||
GJA1 | ENST00000649003.1 | c.47C>G | p.Ala16Gly | missense_variant | Exon 2 of 2 | ENSP00000497283.1 | ||||
GJA1 | ENST00000650427.1 | c.47C>G | p.Ala16Gly | missense_variant | Exon 2 of 2 | ENSP00000497367.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251402Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135884
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461508Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727108
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: GJA1 c.47C>G (p.Ala16Gly) results in a non-conservative amino acid change located in the Connexin, N-terminal domain (IPR013092) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251402 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.47C>G in individuals affected with Oculodentodigital Dysplasia and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at