NM_001047.4:c.19G>C

Variant names:

• chr5-6633595-G-C
• rs1455031515
• NM_001047.4:c.19G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001047.4(SRD5A1):​c.19G>C​(p.Val7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SRD5A1 NM_001047.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045223713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.19G>C	p.Val7Leu	missense_variant	Exon 1 of 5	ENST00000274192.7	NP_001038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.19G>C	p.Val7Leu	missense_variant	Exon 1 of 5	1	NM_001047.4	ENSP00000274192.5
SRD5A1	ENST00000504286.1	n.140G>C		non_coding_transcript_exon_variant	Exon 1 of 3	2		ENSP00000518753.1
SRD5A1	ENST00000510531.5	n.19G>C		non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000425330.1
SRD5A1	ENST00000513117.1	n.19G>C		non_coding_transcript_exon_variant	Exon 1 of 4	2		ENSP00000421342.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.1
DANN	Benign	0.51
DEOGEN2	Benign	0.053	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.00080	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.93	N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.022
Sift	Benign	0.59	T
Sift4G	Benign	0.91	T
Polyphen		0.0	B
Vest4		0.090
MutPred		0.22		Loss of catalytic residue at V7 (P = 0.0213);
MVP		0.14
MPC		0.50
ClinPred		0.088	T
GERP RS		0.38
Varity_R		0.057
gMVP		0.23

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: rs1455031515; hg19: chr5-6633708;