chr17-40363058-C-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_152219.4(GJD3):c.758G>C(p.Arg253Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 1,231,732 control chromosomes in the GnomAD database, including 317 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Consequence
NM_152219.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GJD3 | NM_152219.4 | c.758G>C | p.Arg253Pro | missense_variant | Exon 1 of 1 | ENST00000578689.2 | NP_689343.3 | |
GJD3-AS1 | NR_186704.1 | n.214C>G | non_coding_transcript_exon_variant | Exon 1 of 1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0152 AC: 2288AN: 150734Hom.: 31 Cov.: 32
GnomAD3 exomes AF: 0.0321 AC: 12AN: 374Hom.: 1 AF XY: 0.0229 AC XY: 5AN XY: 218
GnomAD4 exome AF: 0.0223 AC: 24086AN: 1080888Hom.: 286 Cov.: 33 AF XY: 0.0224 AC XY: 11489AN XY: 513114
GnomAD4 genome AF: 0.0152 AC: 2287AN: 150844Hom.: 31 Cov.: 32 AF XY: 0.0154 AC XY: 1133AN XY: 73716
ClinVar
Submissions by phenotype
Meniere disease Benign:1
The NC_000017.11:g.40363058C>G, is a missense variant in GJD3 gene which produces an amino acid change from arginine to proline in the cytoplasmatic region of the connexon. The variant is part of an haplotype involved in Meniere’s Disease, composed by g.40356228C>T, g.40363058C>G, g.40363293G>A, g.40363294C>G and g.40363579G>T. The haplotype was found in 10 individuals with familial Meniere’s Disease, segregating in 3 of these families (PP1); and in another 8 individuals with sporadic Meniere’s Disease. GnomAD exomes allele frequency = 0.0223 is greater than 0.0001 (BS1); however, the frequency of the haplotype for the Iberian population in Spain is 0.0093. The variant was observed in healthy adults in gnomAD (BS2). The MetaRNN value of the variant is 0.0041 (BP4). In summary, this variant meets the criteria to be classified as likely benign based on the ACMG/AMP criteria applied: PP1,BS1,BS2,BP4. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at