5-6633811-C-T

Variant names:

• chr5-6633811-C-T
• rs199742160
• NM_001047.4:c.235C>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.235C>T​(p.Leu79Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SRD5A1 NM_001047.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.879

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=0.10021809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.235C>T	p.Leu79Phe	missense_variant	Exon 1 of 5	ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.261C>T	p.Val87Val	synonymous_variant	Exon 1 of 4		NP_001311251.1
SRD5A1	NM_001324323.2	c.-487C>T		5_prime_UTR_variant	Exon 1 of 6		NP_001311252.1
SRD5A1	NR_136739.2	n.372C>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.235C>T	p.Leu79Phe	missense_variant	Exon 1 of 5	1	NM_001047.4	ENSP00000274192.5
SRD5A1	ENST00000504286.1	n.356C>T		non_coding_transcript_exon_variant	Exon 1 of 3	2		ENSP00000518753.1
SRD5A1	ENST00000510531.5	n.235C>T		non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000425330.1
SRD5A1	ENST00000513117.1	n.235C>T		non_coding_transcript_exon_variant	Exon 1 of 4	2		ENSP00000421342.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000445 AC: 1 AN: 224816 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 124504

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000985

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445574 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 719562

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.049
Sift	Benign	0.048	D
Sift4G	Benign	0.081	T
Polyphen		0.069	B
Vest4		0.091
MutPred		0.23		Gain of helix (P = 0.0425);
MVP		0.31
MPC		0.66
ClinPred		0.12	T
GERP RS		2.9
Varity_R		0.12
gMVP		0.20

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: rs199742160; hg19: chr5-6633924;