chr18-63350953-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_002035.4(KDSR):c.544G>A(p.Gly182Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,828 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 Likely pathogenic (★).
Frequency
Consequence
NM_002035.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KDSR | NM_002035.4 | c.544G>A | p.Gly182Ser | missense_variant | Exon 6 of 10 | ENST00000645214.2 | NP_002026.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251324Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135832
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461828Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727218
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Erythrokeratodermia variabilis et progressiva 4 Pathogenic:1
The homozygous missense variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Functional studies provide moderate evidence of having a damaging effect on the gene or gene product (PMID: 28774589). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.84; 3Cnet: 0.21). The same nucleotide change resulting in the same amino acid change has been previously reported to be associated with KDSR-related disorder (PMID: 28774589). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at