4-55369693-T-C

Variant names:

• chr4-55369693-T-C
• rs819267
• NM_024592.5:c.698-139T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.766
• Publications: 3 publications found

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]

ENSG00000288695 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024592.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A3	NM_024592.5	MANE Select	c.698-139T>C		intron	N/A	NP_078868.1
	SRD5A3	NM_001410732.1		c.563-139T>C		intron	N/A	NP_001397661.1
	SRD5A3-AS1	NR_037969.1		n.364-2530A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A3	ENST00000264228.9	TSL:1 MANE Select	c.698-139T>C		intron	N/A	ENSP00000264228.4
	ENSG00000288695	ENST00000679707.1		c.563-1981T>C		intron	N/A	ENSP00000505713.1
	SRD5A3-AS1	ENST00000433175.6	TSL:1	n.269-2530A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42454 AN: 150468 Hom.: 6219 Cov.: 29

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.: 11 AF XY: 0.297 AC XY: 127017 AN XY: 428126

African (AFR) AF: 0.258 AC: 5099 AN: 19748

American (AMR) AF: 0.237 AC: 6821 AN: 28728

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 4663 AN: 18894

East Asian (EAS) AF: 0.129 AC: 4356 AN: 33688

South Asian (SAS) AF: 0.392 AC: 23417 AN: 59784

European-Finnish (FIN) AF: 0.358 AC: 12865 AN: 35926

Middle Eastern (MID) AF: 0.245 AC: 670 AN: 2740

European-Non Finnish (NFE) AF: 0.293 AC: 173352 AN: 591544

Other (OTH) AF: 0.277 AC: 10786 AN: 38882

GnomAD4 genome AF: 0.282 AC: 42482 AN: 150576 Hom.: 6226 Cov.: 29 AF XY: 0.287 AC XY: 21051 AN XY: 73408

African (AFR) AF: 0.256 AC: 10469 AN: 40872

American (AMR) AF: 0.256 AC: 3863 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 861 AN: 3464

East Asian (EAS) AF: 0.104 AC: 532 AN: 5094

South Asian (SAS) AF: 0.401 AC: 1916 AN: 4782

European-Finnish (FIN) AF: 0.384 AC: 3909 AN: 10188

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.296 AC: 20038 AN: 67788

Other (OTH) AF: 0.267 AC: 556 AN: 2084

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

Submissions by phenotype

not provided Benign:1

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.5
DANN	Benign	0.63
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs819267; hg19: chr4-56235860;