4-55364215-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_024592.5(SRD5A3):āc.506A>Gā(p.Tyr169Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,976 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_024592.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SRD5A3 | NM_024592.5 | c.506A>G | p.Tyr169Cys | missense_variant | Exon 3 of 5 | ENST00000264228.9 | NP_078868.1 | |
SRD5A3 | NM_001410732.1 | c.506A>G | p.Tyr169Cys | missense_variant | Exon 3 of 4 | NP_001397661.1 | ||
SRD5A3 | XM_017008601.2 | c.371A>G | p.Tyr124Cys | missense_variant | Exon 3 of 5 | XP_016864090.1 | ||
SRD5A3 | XM_005265767.4 | c.364+4727A>G | intron_variant | Intron 2 of 2 | XP_005265824.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SRD5A3 | ENST00000264228.9 | c.506A>G | p.Tyr169Cys | missense_variant | Exon 3 of 5 | 1 | NM_024592.5 | ENSP00000264228.4 | ||
ENSG00000288695 | ENST00000679707.1 | c.506A>G | p.Tyr169Cys | missense_variant | Exon 3 of 6 | ENSP00000505713.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152088Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251460Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135904
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727244
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152088Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74274
ClinVar
Submissions by phenotype
Kahrizi syndrome Pathogenic:1
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SRD5A3-congenital disorder of glycosylation Uncertain:1
This novel homozygous variant has been identified in a proband with global developmental delay, deep set eyes, nystagmus, bilateral epicanthal folds, temporal balding, flapping of hands, happy demeanor, self absorbed. This variant has been identified in 0.0028% in gnomAD (aggregated) (PM2_moderate). -
not provided Uncertain:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21937992) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at