2-31526257-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000348.4(SRD5A2):​c.704A>C​(p.Tyr235Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000701 in 1,425,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 7.0e-7 ( 0 hom. )

Consequence

SRD5A2
NM_000348.4 missense

Scores

5
2
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.00
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.855

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRD5A2NM_000348.4 linkc.704A>C p.Tyr235Ser missense_variant Exon 5 of 5 ENST00000622030.2 NP_000339.2 P31213
SRD5A2XM_011533069.3 linkc.482A>C p.Tyr161Ser missense_variant Exon 5 of 5 XP_011531371.1
SRD5A2XM_011533072.3 linkc.449A>C p.Tyr150Ser missense_variant Exon 7 of 7 XP_011531374.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRD5A2ENST00000622030.2 linkc.704A>C p.Tyr235Ser missense_variant Exon 5 of 5 1 NM_000348.4 ENSP00000477587.1 P31213

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.01e-7
AC:
1
AN:
1425548
Hom.:
0
Cov.:
28
AF XY:
0.00000142
AC XY:
1
AN XY:
706398
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000123
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.72
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.17
CADD
Pathogenic
29
DANN
Benign
0.89
FATHMM_MKL
Pathogenic
0.99
D
MetaRNN
Pathogenic
0.86
D
PrimateAI
Uncertain
0.66
T
Sift4G
Uncertain
0.0040
D
Vest4
0.92
MVP
0.59
GERP RS
5.8
gMVP
0.99

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-31751327; API