Variant rs201175894 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM5PP5

The NM_000348.4(SRD5A2):c.271T>G(p.Tyr91Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000363 in 1,569,840 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y91H) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 37)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

SRD5A2
NM_000348.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.10

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]

SRD5A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM1

In a chain 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (size 253) in uniprot entity S5A2_HUMAN there are 57 pathogenic changes around while only 18 benign (76%) in NM_000348.4

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr2-31580630-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 492899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

PP5

Variant 2-31580630-A-C is Pathogenic according to our data. Variant chr2-31580630-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 492898.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A2	NM_000348.4 linkuse as main transcript	c.271T>G	p.Tyr91Asp	missense_variant	1/5	ENST00000622030.2
SRD5A2	XM_011533072.3 linkuse as main transcript	c.27-46864T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A2	ENST00000622030.2 linkuse as main transcript	c.271T>G	p.Tyr91Asp	missense_variant	1/5	1	NM_000348.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000808

AC:

AN:

197920

Hom.:

AF XY:

0.0000557

AC XY:

AN XY:

107712

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000388

AC:

AN:

1417588

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

701928

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00178

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000365

Gnomad4 OTH exome

AF:

0.000102

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000523

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000335

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital

Sep 27, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

Cadd

Pathogenic

Dann

Benign

0.82

FATHMM_MKL

Uncertain

0.91

MetaRNN

Uncertain

0.67

PrimateAI

Uncertain

0.66

Sift4G

Uncertain

0.0020

Vest4

0.92

MVP

0.79

GERP RS

4.0

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over