dbSNP rs3736316: SRD5A1:p.Thr160Thr (chr5-6656097-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001047.4(SRD5A1):c.480G>A(p.Thr160Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,611,670 control chromosomes in the GnomAD database, including 106,769 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 9402 hom., cov: 32)

Exomes 𝑓: 0.36 ( 97367 hom. )

Consequence

SRD5A1
NM_001047.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.27

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP7

Synonymous conserved (PhyloP=-2.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A1	NM_001047.4 link	c.480G>A	p.Thr160Thr	synonymous_variant	Exon 3 of 5	ENST00000274192.7	NP_001038.1	P18405
SRD5A1	NM_001324322.2 link	c.339G>A	p.Thr113Thr	synonymous_variant	Exon 2 of 4		NP_001311251.1	P18405
SRD5A1	NM_001324323.2 link	c.261G>A	p.Thr87Thr	synonymous_variant	Exon 4 of 6		NP_001311252.1	P18405B7Z4D8
SRD5A1	NR_136739.2 link	n.807G>A		non_coding_transcript_exon_variant	Exon 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SRD5A1	ENST00000274192.7 link	c.480G>A	p.Thr160Thr	synonymous_variant	Exon 3 of 5	1	NM_001047.4	ENSP00000274192.5	P18405
SRD5A1	ENST00000510531.5 link	n.*601G>A		non_coding_transcript_exon_variant	Exon 4 of 6	2		ENSP00000425330.1	D6RDL6
SRD5A1	ENST00000513117.1 link	n.313G>A		non_coding_transcript_exon_variant	Exon 2 of 4	2		ENSP00000421342.1	D6RG03
SRD5A1	ENST00000510531.5 link	n.*601G>A		3_prime_UTR_variant	Exon 4 of 6	2		ENSP00000425330.1	D6RDL6

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52794

AN:

151758

Hom.:

9390

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.473

Gnomad AMR

AF:

0.356

Gnomad ASJ

AF:

0.454

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.374

Gnomad OTH

AF:

0.371

GnomAD2 exomes

AF:

0.330

AC:

82832

AN:

250758

AF XY:

0.328

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.334

Gnomad ASJ exome

AF:

0.462

Gnomad EAS exome

AF:

0.172

Gnomad FIN exome

AF:

0.311

Gnomad NFE exome

AF:

0.375

Gnomad OTH exome

AF:

0.360

GnomAD4 exome

AF:

0.359

AC:

524465

AN:

1459794

Hom.:

97367

Cov.:

AF XY:

0.356

AC XY:

258299

AN XY:

726234

show subpopulations

Gnomad4 AFR exome

AF:

0.344

AC:

11488

AN:

33422

Gnomad4 AMR exome

AF:

0.337

AC:

15014

AN:

44576

Gnomad4 ASJ exome

AF:

0.460

AC:

12006

AN:

26100

Gnomad4 EAS exome

AF:

0.164

AC:

6499

AN:

39668

Gnomad4 SAS exome

AF:

0.222

AC:

19146

AN:

86168

Gnomad4 FIN exome

AF:

0.315

AC:

16831

AN:

53358

Gnomad4 NFE exome

AF:

0.378

AC:

419919

AN:

1110420

Gnomad4 Remaining exome

AF:

0.355

AC:

21414

AN:

60326

Heterozygous variant carriers

16072

32145

48217

64290

80362

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

13096

26192

39288

52384

65480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.348

AC:

52846

AN:

151876

Hom.:

9402

Cov.:

AF XY:

0.342

AC XY:

25363

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.338

AC:

0.33777

AN:

0.33777

Gnomad4 AMR

AF:

0.356

AC:

0.355569

AN:

0.355569

Gnomad4 ASJ

AF:

0.454

AC:

0.454414

AN:

0.454414

Gnomad4 EAS

AF:

0.161

AC:

0.160922

AN:

0.160922

Gnomad4 SAS

AF:

0.217

AC:

0.216715

AN:

0.216715

Gnomad4 FIN

AF:

0.308

AC:

0.308065

AN:

0.308065

Gnomad4 NFE

AF:

0.374

AC:

0.373988

AN:

0.373988

Gnomad4 OTH

AF:

0.371

AC:

0.371442

AN:

0.371442

Heterozygous variant carriers

1764

3528

5293

7057

8821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.374

Hom.:

5579

Bravo

AF:

0.355

Asia WGS

AF:

0.189

AC:

659

AN:

3478

EpiCase

AF:

0.389

EpiControl

AF:

0.393

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.19

DANN

Benign

0.91

Mutation Taster

=100/0

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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