dbSNP rs199742160: SRD5A1:p.Leu79Ile (chr5-6633811-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001047.4(SRD5A1):c.235C>A(p.Leu79Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000376 in 1,597,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L79V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SRD5A1
NM_001047.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.879

Publications

0 publications found

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08764765).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001047.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRD5A1	NM_001047.4	MANE Select	c.235C>A	p.Leu79Ile	missense	Exon 1 of 5	NP_001038.1	P18405
SRD5A1	NM_001324322.2		c.261C>A	p.Val87Val	synonymous	Exon 1 of 4	NP_001311251.1
SRD5A1	NM_001324323.2		c.-487C>A		5_prime_UTR	Exon 1 of 6	NP_001311252.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRD5A1	ENST00000274192.7	TSL:1 MANE Select	c.235C>A	p.Leu79Ile	missense	Exon 1 of 5	ENSP00000274192.5	P18405
SRD5A1	ENST00000854432.1		c.235C>A	p.Leu79Ile	missense	Exon 1 of 6	ENSP00000524491.1
SRD5A1	ENST00000854431.1		c.235C>A	p.Leu79Ile	missense	Exon 1 of 5	ENSP00000524490.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000445

AC:

AN:

224816

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000700

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000208

AC:

AN:

1445574

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719562

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33426

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26096

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37814

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111636

Other (OTH)

AF:

0.00

AC:

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000197

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41478

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000839

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.46

M_CAP

Benign

0.013

MetaRNN

Benign

0.088

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

0.88

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.65

REVEL

Benign

0.039

Sift

Benign

0.20

Sift4G

Benign

0.24

Polyphen

0.025

Vest4

0.26

MutPred

0.22

Loss of glycosylation at P77 (P = 0.1379)

MVP

0.37

MPC

0.63

ClinPred

0.076

GERP RS

2.9

PromoterAI

0.0085

Neutral

(source)

Varity_R

0.11

gMVP

0.14

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over