5-6656126-A-T

Position:

• chr5-6656126-A-T

Variant summary

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

The NM_001047.4(SRD5A1):​c.509A>T​(p.His170Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SRD5A1 NM_001047.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01

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]

SRD5A1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.509A>T	p.His170Leu	missense_variant	3/5	ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.368A>T	p.His123Leu	missense_variant	2/4		NP_001311251.1
SRD5A1	NM_001324323.2	c.290A>T	p.His97Leu	missense_variant	4/6		NP_001311252.1
SRD5A1	NR_136739.2	n.836A>T		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.509A>T	p.His170Leu	missense_variant	3/5	1	NM_001047.4	ENSP00000274192.5
SRD5A1	ENST00000510531.5	n.*630A>T		non_coding_transcript_exon_variant	4/6	2		ENSP00000425330.1
SRD5A1	ENST00000513117.1	n.342A>T		non_coding_transcript_exon_variant	2/4	2		ENSP00000421342.1
SRD5A1	ENST00000510531.5	n.*630A>T		3_prime_UTR_variant	4/6	2		ENSP00000425330.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

The c.509A>T (p.H170L) alteration is located in exon 3 (coding exon 3) of the SRD5A1 gene. This alteration results from a A to T substitution at nucleotide position 509, causing the histidine (H) at amino acid position 170 to be replaced by a leucine (L). 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	0.32
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Uncertain	0.75	D
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0047	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-7.8	D
REVEL	Benign	0.22
Sift	Uncertain	0.019	D
Sift4G	Benign	0.13	T
Polyphen		0.024	B
Vest4		0.73
MutPred		0.36		Loss of disorder (P = 0.0398);
MVP		0.65
MPC		0.98
ClinPred		0.96	D
GERP RS		3.5
Varity_R		0.63
gMVP		0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-6656239;