Variant 5-6633811-C-G 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.235C>G(p.Leu79Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00003 in 1,597,822 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: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

SRD5A1
NM_001047.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.879

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 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=0.1053243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SRD5A1	NM_001047.4 linkuse as main transcript	c.235C>G	p.Leu79Val	missense_variant	1/5	ENST00000274192.7
SRD5A1	NM_001324322.2 linkuse as main transcript	c.261C>G	p.Val87=	synonymous_variant	1/4
SRD5A1	NM_001324323.2 linkuse as main transcript	c.-487C>G		5_prime_UTR_variant	1/6
SRD5A1	NR_136739.2 linkuse as main transcript	n.372C>G		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.235C>G	p.Leu79Val	missense_variant	1/5	1	NM_001047.4	P1
SRD5A1	ENST00000504286.2 linkuse as main transcript	c.235C>G	p.Leu79Val	missense_variant, NMD_transcript_variant	1/6	2
SRD5A1	ENST00000513117.1 linkuse as main transcript	c.235C>G	p.Leu79Val	missense_variant, NMD_transcript_variant	1/4	2
SRD5A1	ENST00000510531.6 linkuse as main transcript	c.235C>G	p.Leu79Val	missense_variant, NMD_transcript_variant	1/6	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000304

AC:

AN:

1445574

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

719562

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000333

Gnomad4 OTH exome

AF:

0.0000996

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

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

Dec 03, 2021

The c.235C>G (p.L79V) alteration is located in exon 1 (coding exon 1) of the SRD5A1 gene. This alteration results from a C to G substitution at nucleotide position 235, causing the leucine (L) at amino acid position 79 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

0.22

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.47

M_CAP

Benign

0.019

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.2

REVEL

Benign

0.059

Sift

Benign

0.17

Sift4G

Benign

0.25

Polyphen

0.15

Vest4

0.20

MutPred

0.22

Loss of glycosylation at P77 (P = 0.1015);

MVP

0.33

MPC

0.60

ClinPred

0.51

GERP RS

2.9

Varity_R

0.12

gMVP

0.22

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