Variant 4-55346365-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5

The NM_024592.5(SRD5A3):c.29C>A(p.Ser10Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SRD5A3
NM_024592.5 stop_gained

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -0.273

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 8 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 4-55346365-C-A is Pathogenic according to our data. Variant chr4-55346365-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 18408.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-55346365-C-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SRD5A3	NM_024592.5 linkuse as main transcript	c.29C>A	p.Ser10Ter	stop_gained	1/5	ENST00000264228.9	NP_078868.1
SRD5A3	NM_001410732.1 linkuse as main transcript	c.29C>A	p.Ser10Ter	stop_gained	1/4		NP_001397661.1
SRD5A3	XM_005265767.4 linkuse as main transcript	c.29C>A	p.Ser10Ter	stop_gained	1/3		XP_005265824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SRD5A3	ENST00000264228.9 linkuse as main transcript	c.29C>A	p.Ser10Ter	stop_gained	1/5	1	NM_024592.5	ENSP00000264228	P1
SRD5A3	ENST00000679836.1 linkuse as main transcript	c.29C>A	p.Ser10Ter	stop_gained	1/4			ENSP00000506601
SRD5A3	ENST00000505210.1 linkuse as main transcript			upstream_gene_variant		3		ENSP00000424714

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1389190

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

687248

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SRD5A3-congenital disorder of glycosylation

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 23, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Benign

0.95

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.011

MutationTaster

Benign

1.0

Vest4

0.049

GERP RS

-4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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