4-55349464-C-G

Position:

• chr4-55349464-C-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRD5A3	NM_024592.5	c.221+2907C>G		intron_variant		ENST00000264228.9	NP_078868.1
SRD5A3	NM_001410732.1	c.221+2907C>G		intron_variant			NP_001397661.1
SRD5A3	XM_005265767.4	c.221+2907C>G		intron_variant			XP_005265824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRD5A3	ENST00000264228.9	c.221+2907C>G		intron_variant		1	NM_024592.5	ENSP00000264228.4
ENSG00000288695	ENST00000679707.1	c.221+2907C>G		intron_variant				ENSP00000505713.1

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

Gnomad4 AFR AF: 0.0631

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.281

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.81
DANN	Benign	0.53

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: rs11133373; hg19: chr4-56215631;