5-6669649-T-C

Position:

• chr5-6669649-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001047.4(SRD5A1):​c.*1381T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,114 control chromosomes in the GnomAD database, including 16,318 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 0.46 (16318 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: SRD5A1 NM_001047.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441

Genes affected

SRD5A1 (HGNC:11284): (steroid 5 alpha-reductase 1) Steroid 5-alpha-reductase (EC 1.3.99.5) catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT). Also see SRD5A2 (MIM 607306).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A1	NM_001047.4	c.*1381T>C		3_prime_UTR_variant	5/5	ENST00000274192.7
SRD5A1	NM_001324322.2	c.*1381T>C		3_prime_UTR_variant	4/4
SRD5A1	NM_001324323.2	c.*1381T>C		3_prime_UTR_variant	6/6
SRD5A1	NR_136739.2	n.2488T>C		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A1	ENST00000274192.7	c.*1381T>C		3_prime_UTR_variant	5/5	1	NM_001047.4	P1
SRD5A1	ENST00000504286.2	c.*1586T>C		3_prime_UTR_variant, NMD_transcript_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69572 AN: 151996 Hom.: 16308 Cov.: 33

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.438

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.458 AC: 69626 AN: 152114 Hom.: 16318 Cov.: 33 AF XY: 0.455 AC XY: 33809 AN XY: 74356

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.435

Alfa AF: 0.432 Hom.: 21041

Bravo AF: 0.469

Asia WGS AF: 0.401 AC: 1396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.49

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: rs39848; hg19: chr5-6669762;