Variant 5-6633731-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001047.4(SRD5A1):c.155C>T(p.Ala52Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000416 in 1,442,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

SRD5A1
NM_001047.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0450

Variant links:

Genes affected

SRD5A1 (HGNC:11284): (steroid 5 alpha-reductase 1) Steroid 5-alpha-reductase (EC 1.3.99.5) catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT). Also see SRD5A2 (MIM 607306).[supplied by OMIM, Mar 2008]

SRD5A1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19324401).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SRD5A1	NM_001047.4 linkuse as main transcript	c.155C>T	p.Ala52Val	missense_variant	1/5	ENST00000274192.7
SRD5A1	NM_001324322.2 linkuse as main transcript	c.181C>T	p.Arg61Cys	missense_variant	1/4
SRD5A1	NM_001324323.2 linkuse as main transcript	c.-567C>T		5_prime_UTR_variant	1/6
SRD5A1	NR_136739.2 linkuse as main transcript	n.292C>T		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SRD5A1	ENST00000274192.7 linkuse as main transcript	c.155C>T	p.Ala52Val	missense_variant	1/5	1	NM_001047.4	P1
SRD5A1	ENST00000504286.2 linkuse as main transcript	c.155C>T	p.Ala52Val	missense_variant, NMD_transcript_variant	1/6	2
SRD5A1	ENST00000513117.1 linkuse as main transcript	c.155C>T	p.Ala52Val	missense_variant, NMD_transcript_variant	1/4	2
SRD5A1	ENST00000510531.6 linkuse as main transcript	c.155C>T	p.Ala52Val	missense_variant, NMD_transcript_variant	1/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000416

AC:

AN:

1442028

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

717442

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2022

The c.155C>T (p.A52V) alteration is located in exon 1 (coding exon 1) of the SRD5A1 gene. This alteration results from a C to T substitution at nucleotide position 155, causing the alanine (A) at amino acid position 52 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.29

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.2

REVEL

Benign

0.049

Sift

Benign

0.23

Sift4G

Benign

0.22

Polyphen

0.59

Vest4

0.14

MutPred

0.45

Loss of methylation at R53 (P = 0.0972);

MVP

0.55

MPC

0.55

ClinPred

0.30

GERP RS

2.8

Varity_R

0.094

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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