4-55364157-G-T

Variant names:

• chr4-55364157-G-T
• rs151267741
• NM_024592.5:c.448G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024592.5(SRD5A3):​c.448G>T​(p.Val150Phe) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRD5A3 NM_024592.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.47

Genes affected

SRD5A3 (HGNC:25812): (steroid 5 alpha-reductase 3) The protein encoded by this gene belongs to the steroid 5-alpha reductase family, and polyprenol reductase subfamily. It is involved in the production of androgen 5-alpha-dihydrotestosterone (DHT) from testosterone, and maintenance of the androgen-androgen receptor activation pathway. This protein is also necessary for the conversion of polyprenol into dolichol, which is required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-linked glycosylation of proteins. Mutations in this gene are associated with congenital disorder of glycosylation type Iq. [provided by RefSeq, Mar 2011]

ENSG00000288695 (HGNC:):

SRD5A3-AS1 (HGNC:44138): (SRD5A3 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.848

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A3	NM_024592.5	c.448G>T	p.Val150Phe	missense_variant	Exon 3 of 5	ENST00000264228.9	NP_078868.1
SRD5A3	NM_001410732.1	c.448G>T	p.Val150Phe	missense_variant	Exon 3 of 4		NP_001397661.1
SRD5A3	XM_017008601.2	c.313G>T	p.Val105Phe	missense_variant	Exon 3 of 5		XP_016864090.1
SRD5A3	XM_005265767.4	c.364+4669G>T		intron_variant	Intron 2 of 2		XP_005265824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A3	ENST00000264228.9	c.448G>T	p.Val150Phe	missense_variant	Exon 3 of 5	1	NM_024592.5	ENSP00000264228.4
ENSG00000288695	ENST00000679707.1	c.448G>T	p.Val150Phe	missense_variant	Exon 3 of 6			ENSP00000505713.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251462 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135904

Gnomad AFR exome AF: 0.0000615

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.81
MutPred		0.55		Gain of helix (P = 0.1736);
MVP		0.81
MPC		0.87
ClinPred		0.96	D
GERP RS		2.3
Varity_R		0.50
gMVP		0.89

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: rs151267741; hg19: chr4-56230324;