rs767564684
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000348.4(SRD5A2):c.620C>T(p.Ala207Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
SRD5A2
NM_000348.4 missense
NM_000348.4 missense
Scores
5
3
Clinical Significance
Conservation
PhyloP100: 8.00
Genes affected
SRD5A2 (HGNC:11285): (steroid 5 alpha-reductase 2) This gene encodes a microsomal protein expressed at high levels in androgen-sensitive tissues such as the prostate. The encoded protein is active at acidic pH and is sensitive to the 4-azasteroid inhibitor finasteride. Deficiencies in this gene can result in male pseudohermaphroditism, specifically pseudovaginal perineoscrotal hypospadias (PPSH). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SRD5A2 | NM_000348.4 | c.620C>T | p.Ala207Val | missense_variant | 4/5 | ENST00000622030.2 | NP_000339.2 | |
SRD5A2 | XM_011533069.3 | c.398C>T | p.Ala133Val | missense_variant | 4/5 | XP_011531371.1 | ||
SRD5A2 | XM_011533072.3 | c.365C>T | p.Ala122Val | missense_variant | 6/7 | XP_011531374.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SRD5A2 | ENST00000622030.2 | c.620C>T | p.Ala207Val | missense_variant | 4/5 | 1 | NM_000348.4 | ENSP00000477587.1 | ||
ENSG00000228563 | ENST00000435713.1 | n.255+1685G>A | intron_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Neuberg Centre For Genomic Medicine, NCGM | Jun 22, 2023 | The observed missense variant c.620C>T(p.Thr207Ile) in SRD5A2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.620C>T(p.Thr207Ile) variant is reported with 0.0004% allele frequency in gnomAD Exomes. It has been submitted to ClinVar as Pathogenic/Likely Pathogenic. However, no details are available for independent assessment. The variant is predicted to be damaging by SIFT. The amino acid Thr at position 207 is changed to a Ile changing protein sequence and it might alter its composition and physico-chemical properties. The reference amino acid p.Thr207Ile in SRD5A2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
FATHMM_MKL
Uncertain
D
MetaRNN
Uncertain
D
PrimateAI
Uncertain
T
Sift4G
Benign
T
Vest4
MVP
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.