Variant 4-55369693-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_024592.5(SRD5A3):c.698-139T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 980,510 control chromosomes in the GnomAD database, including 43,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 6226 hom., cov: 29)

Exomes 𝑓: 0.29 ( 36922 hom. )

Consequence

SRD5A3
NM_024592.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.766

Variant links:

Genes affected

SRD5A3 (HGNC:25812): (steroid 5 alpha-reductase 3) The protein encoded by this gene belongs to the steroid 5-alpha reductase family, and polyprenol reductase subfamily. It is involved in the production of androgen 5-alpha-dihydrotestosterone (DHT) from testosterone, and maintenance of the androgen-androgen receptor activation pathway. This protein is also necessary for the conversion of polyprenol into dolichol, which is required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-linked glycosylation of proteins. Mutations in this gene are associated with congenital disorder of glycosylation type Iq. [provided by RefSeq, Mar 2011]

SRD5A3 links:

SRD5A3-AS1 (HGNC:44138): (SRD5A3 antisense RNA 1)

SRD5A3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 4-55369693-T-C is Benign according to our data. Variant chr4-55369693-T-C is described in ClinVar as [Benign]. Clinvar id is 676204.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A3	NM_024592.5 linkuse as main transcript	c.698-139T>C		intron_variant		ENST00000264228.9
SRD5A3-AS1	NR_037969.1 linkuse as main transcript	n.364-2530A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A3	ENST00000264228.9 linkuse as main transcript	c.698-139T>C		intron_variant		1	NM_024592.5	P1

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42454

AN:

150468

Hom.:

6219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.290

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.399

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.296

Gnomad OTH

AF:

0.269

GnomAD4 exome

AF:

0.292

AC:

242029

AN:

829934

Hom.:

36922

Cov.:

AF XY:

0.297

AC XY:

127017

AN XY:

428126

show subpopulations

Gnomad4 AFR exome

AF:

0.258

Gnomad4 AMR exome

AF:

0.237

Gnomad4 ASJ exome

AF:

0.247

Gnomad4 EAS exome

AF:

0.129

Gnomad4 SAS exome

AF:

0.392

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.293

Gnomad4 OTH exome

AF:

0.277

GnomAD4 genome

AF:

0.282

AC:

42482

AN:

150576

Hom.:

6226

Cov.:

AF XY:

0.287

AC XY:

21051

AN XY:

73408

show subpopulations

Gnomad4 AFR

AF:

0.256

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.104

Gnomad4 SAS

AF:

0.401

Gnomad4 FIN

AF:

0.384

Gnomad4 NFE

AF:

0.296

Gnomad4 OTH

AF:

0.267

Alfa

AF:

0.178

Hom.:

409

Bravo

AF:

0.261

Asia WGS

AF:

0.283

AC:

986

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.5

DANN

Benign

0.63

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