chr4-55346386-C-A

Variant names:

• chr4-55346386-C-A
• NM_024592.5:c.50C>A

Variant summary

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

The NM_024592.5(SRD5A3):​c.50C>A​(p.Ala17Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000281 in 1,422,676 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: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: SRD5A3 NM_024592.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313

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:):

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=0.25352645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A3	NM_024592.5	c.50C>A	p.Ala17Glu	missense_variant	Exon 1 of 5	ENST00000264228.9	NP_078868.1
SRD5A3	NM_001410732.1	c.50C>A	p.Ala17Glu	missense_variant	Exon 1 of 4		NP_001397661.1
SRD5A3	XM_005265767.4	c.50C>A	p.Ala17Glu	missense_variant	Exon 1 of 3		XP_005265824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A3	ENST00000264228.9	c.50C>A	p.Ala17Glu	missense_variant	Exon 1 of 5	1	NM_024592.5	ENSP00000264228.4
ENSG00000288695	ENST00000679707.1	c.50C>A	p.Ala17Glu	missense_variant	Exon 1 of 6			ENSP00000505713.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000281 AC: 4 AN: 1422676 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 705984

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: 0.00000365

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.10
Sift	Benign	0.040	D
Sift4G	Benign	0.061	T
Polyphen		0.81	P
Vest4		0.38
MutPred		0.47		Loss of glycosylation at P14 (P = 0.0767);
MVP		0.43
MPC		0.60
ClinPred		0.71	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.25
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr4-56212553;