Genetic Variant NM_001047.4:c.64G>T (chr5-6633640-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001047.4(SRD5A1):c.64G>T(p.Ala22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000257 in 1,556,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SRD5A1
NM_001047.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.878

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=0.0823226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A1	NM_001047.4 link	c.64G>T	p.Ala22Ser	missense_variant	Exon 1 of 5	ENST00000274192.7	NP_001038.1	P18405
SRD5A1	NM_001324322.2 link	c.90G>T	p.Ala30Ala	synonymous_variant	Exon 1 of 4		NP_001311251.1	P18405
SRD5A1	NM_001324323.2 link	c.-658G>T		5_prime_UTR_variant	Exon 1 of 6		NP_001311252.1	P18405B7Z4D8
SRD5A1	NR_136739.2 link	n.201G>T		non_coding_transcript_exon_variant	Exon 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SRD5A1	ENST00000274192.7 link	c.64G>T	p.Ala22Ser	missense_variant	Exon 1 of 5	1	NM_001047.4	ENSP00000274192.5	P18405
SRD5A1	ENST00000504286.1 link	n.185G>T		non_coding_transcript_exon_variant	Exon 1 of 3	2		ENSP00000518753.1
SRD5A1	ENST00000510531.5 link	n.64G>T		non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000425330.1	D6RDL6
SRD5A1	ENST00000513117.1 link	n.64G>T		non_coding_transcript_exon_variant	Exon 1 of 4	2		ENSP00000421342.1	D6RG03

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

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:

0.000478

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1403728

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

695164

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:

0.00000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.2

DANN

Benign

0.94

DEOGEN2

Benign

0.15

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.40

M_CAP

Benign

0.021

MetaRNN

Benign

0.082

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.98

REVEL

Benign

0.060

Sift

Benign

0.50

Sift4G

Benign

0.51

Polyphen

0.41

Vest4

0.18

MutPred

0.48

Loss of helix (P = 0.0167);

MVP

0.17

MPC

0.48

ClinPred

0.29

GERP RS

-1.4

Varity_R

0.049

gMVP

0.42

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over