5-6633731-C-T

Variant names:

• chr5-6633731-C-T
• rs948067541
• NM_001047.4:c.155C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001047.4(SRD5A1):​c.155C>T​(p.Ala52Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000416 in 1,442,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: SRD5A1 NM_001047.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0450

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19324401).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.155C>T	p.Ala52Val	missense_variant	Exon 1 of 5	ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.181C>T	p.Arg61Cys	missense_variant	Exon 1 of 4		NP_001311251.1
SRD5A1	NM_001324323.2	c.-567C>T		5_prime_UTR_variant	Exon 1 of 6		NP_001311252.1
SRD5A1	NR_136739.2	n.292C>T		non_coding_transcript_exon_variant	Exon 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.155C>T	p.Ala52Val	missense_variant	Exon 1 of 5	1	NM_001047.4	ENSP00000274192.5
SRD5A1	ENST00000504286.1	n.276C>T		non_coding_transcript_exon_variant	Exon 1 of 3	2		ENSP00000518753.1
SRD5A1	ENST00000510531.5	n.155C>T		non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000425330.1
SRD5A1	ENST00000513117.1	n.155C>T		non_coding_transcript_exon_variant	Exon 1 of 4	2		ENSP00000421342.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000416 AC: 6 AN: 1442028 Hom.: 0 Cov.: 35 AF XY: 0.00000279 AC XY: 2 AN XY: 717442

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.155C>T (p.A52V) alteration is located in exon 1 (coding exon 1) of the SRD5A1 gene. This alteration results from a C to T substitution at nucleotide position 155, causing the alanine (A) at amino acid position 52 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.049
Sift	Benign	0.23	T
Sift4G	Benign	0.22	T
Polyphen		0.59	P
Vest4		0.14
MutPred		0.45		Loss of methylation at R53 (P = 0.0972);
MVP		0.55
MPC		0.55
ClinPred		0.30	T
GERP RS		2.8
Varity_R		0.094
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs948067541; hg19: chr5-6633844;