4-55364157-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_024592.5(SRD5A3):c.448G>A(p.Val150Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000675 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_024592.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SRD5A3 | NM_024592.5 | c.448G>A | p.Val150Ile | missense_variant | Exon 3 of 5 | ENST00000264228.9 | NP_078868.1 | |
SRD5A3 | NM_001410732.1 | c.448G>A | p.Val150Ile | missense_variant | Exon 3 of 4 | NP_001397661.1 | ||
SRD5A3 | XM_017008601.2 | c.313G>A | p.Val105Ile | missense_variant | Exon 3 of 5 | XP_016864090.1 | ||
SRD5A3 | XM_005265767.4 | c.364+4669G>A | 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.448G>A | p.Val150Ile | missense_variant | Exon 3 of 5 | 1 | NM_024592.5 | ENSP00000264228.4 | ||
ENSG00000288695 | ENST00000679707.1 | c.448G>A | p.Val150Ile | missense_variant | Exon 3 of 6 | ENSP00000505713.1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000115 AC: 29AN: 251462Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135904
GnomAD4 exome AF: 0.0000677 AC: 99AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.0000729 AC XY: 53AN XY: 727248
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74332
ClinVar
Submissions by phenotype
SRD5A3-congenital disorder of glycosylation Uncertain:2
This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 150 of the SRD5A3 protein (p.Val150Ile). This variant is present in population databases (rs151267741, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with SRD5A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 903285). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SRD5A3 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Inborn genetic diseases Uncertain:1
The c.448G>A (p.V150I) alteration is located in exon 3 (coding exon 3) of the SRD5A3 gene. This alteration results from a G to A substitution at nucleotide position 448, causing the valine (V) at amino acid position 150 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at