4-55349464-C-G

Variant names:

• chr4-55349464-C-G
• rs11133373
• NM_024592.5:c.221+2907C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024592.5(SRD5A3):​c.221+2907C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,808 control chromosomes in the GnomAD database, including 7,001 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (7001 hom., cov: 32)
• Consequence: SRD5A3 NM_024592.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.979
• Publications: 27 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]

SRD5A3 Gene-Disease associations (from GenCC):

• SRD5A3-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000288695 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 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.221+2907C>G		intron	N/A	NP_078868.1
	SRD5A3	NM_001410732.1		c.221+2907C>G		intron	N/A	NP_001397661.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A3	ENST00000264228.9	TSL:1 MANE Select	c.221+2907C>G		intron	N/A	ENSP00000264228.4
	ENSG00000288695	ENST00000679707.1		c.221+2907C>G		intron	N/A	ENSP00000505713.1
	SRD5A3	ENST00000679836.1		c.221+2907C>G		intron	N/A	ENSP00000506601.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40957 AN: 151700 Hom.: 6983 Cov.: 32

Gnomad AFR AF: 0.0633

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.275

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.270 AC: 40986 AN: 151808 Hom.: 7001 Cov.: 32 AF XY: 0.279 AC XY: 20668 AN XY: 74154

African (AFR) AF: 0.0631 AC: 2613 AN: 41418

American (AMR) AF: 0.407 AC: 6218 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1323 AN: 3470

East Asian (EAS) AF: 0.597 AC: 3084 AN: 5164

South Asian (SAS) AF: 0.376 AC: 1809 AN: 4808

European-Finnish (FIN) AF: 0.345 AC: 3605 AN: 10452

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.315 AC: 21386 AN: 67920

Other (OTH) AF: 0.281 AC: 592 AN: 2106

Alfa AF: 0.169 Hom.: 384

Bravo AF: 0.268

Asia WGS AF: 0.452 AC: 1570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.81
DANN	Benign	0.53
PhyloP100		-0.98
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: rs11133373; hg19: chr4-56215631;