rs2538

chr4-55370161-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024592.5(SRD5A3):c.*70C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,590,128 control chromosomes in the GnomAD database, including 68,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6254 hom., cov: 32)
  • Exomes 𝑓: 0.29 (61955 hom.)
• Consequence: SRD5A3 NM_024592.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0430

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

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-55370161-C-T is Benign according to our data. Variant chr4-55370161-C-T is described in ClinVar as [Benign]. Clinvar id is 349009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A3	NM_024592.5	c.*70C>T		3_prime_UTR_variant	5/5	ENST00000264228.9
SRD5A3-AS1	NR_037969.1	n.364-2998G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A3	ENST00000264228.9	c.*70C>T		3_prime_UTR_variant	5/5	1	NM_024592.5	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42644 AN: 151922 Hom.: 6247 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.290 AC: 416747 AN: 1438088 Hom.: 61955 Cov.: 28 AF XY: 0.294 AC XY: 210794 AN XY: 716776

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.244

Gnomad4 EAS exome AF: 0.133

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.355

Gnomad4 NFE exome AF: 0.290

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.281 AC: 42672 AN: 152040 Hom.: 6254 Cov.: 32 AF XY: 0.285 AC XY: 21186 AN XY: 74312

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.263

Alfa AF: 0.284 Hom.: 1950

Bravo AF: 0.261

Asia WGS AF: 0.284 AC: 989 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

SRD5A3-congenital disorder of glycosylation Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.9
Dann	Benign	0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs2538; hg19: chr4-56236328; COSMIC: COSV51711799; COSMIC: COSV51711799;