Variant chr4-55346237-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The ENST00000679836.1(SRD5A3):c.-100C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,124,916 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.010 ( 12 hom., cov: 33)

Exomes 𝑓: 0.013 ( 109 hom. )

Consequence

SRD5A3
ENST00000679836.1 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.0840

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0105 (1598/152224) while in subpopulation AMR AF= 0.0133 (203/15294). AF 95% confidence interval is 0.0125. There are 12 homozygotes in gnomad4. There are 734 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	Effect	MANE
SRD5A3	NM_024592.5 linkuse as main transcript	upstream_gene_variant	ENST00000264228.9
SRD5A3	NM_001410732.1 linkuse as main transcript	upstream_gene_variant
SRD5A3	XM_005265767.4 linkuse as main transcript	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A3	ENST00000679836.1 linkuse as main transcript	c.-100C>G		5_prime_UTR_variant	1/4
SRD5A3	ENST00000264228.9 linkuse as main transcript			upstream_gene_variant		1	NM_024592.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1599

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00905

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0134

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.0414

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.0119

GnomAD4 exome

AF:

0.0129

AC:

12554

AN:

972692

Hom.:

109

Cov.:

AF XY:

0.0128

AC XY:

6044

AN XY:

472600

show subpopulations

Gnomad4 AFR exome

AF:

0.0111

Gnomad4 AMR exome

AF:

0.0116

Gnomad4 ASJ exome

AF:

0.0112

Gnomad4 EAS exome

AF:

0.0000397

Gnomad4 SAS exome

AF:

0.00603

Gnomad4 FIN exome

AF:

0.000675

Gnomad4 NFE exome

AF:

0.0141

Gnomad4 OTH exome

AF:

0.0129

GnomAD4 genome

AF:

0.0105

AC:

1598

AN:

152224

Hom.:

Cov.:

AF XY:

0.00986

AC XY:

734

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00907

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.0133

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.0114

Asia WGS

AF:

0.00231

AC:

AN:

3474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital disorder of glycosylation

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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