rs587670461

Variant names:

• chr1-119507537-C-A
• rs587670461
• NM_000862.3:c.61C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-119507537-C-A
• chr1-119507537-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000862.3(HSD3B1):​c.61C>A​(p.Arg21Ser) 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. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R21C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSD3B1 NM_000862.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

Genes affected

HSD3B1 (HGNC:5217): (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1) The protein encoded by this gene is an enzyme that catalyzes the oxidative conversion of delta-5-3-beta-hydroxysteroid precursors into delta-4-ketosteroids, which leads to the production of all classes of steroid hormones. The encoded protein also catalyzes the interconversion of 3-beta-hydroxy- and 3-keto-5-alpha-androstane steroids. [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3705073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD3B1	NM_000862.3	c.61C>A	p.Arg21Ser	missense_variant	Exon 2 of 4	ENST00000369413.8	NP_000853.1
HSD3B1	NM_001328615.1	c.61C>A	p.Arg21Ser	missense_variant	Exon 2 of 4		NP_001315544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD3B1	ENST00000369413.8	c.61C>A	p.Arg21Ser	missense_variant	Exon 2 of 4	1	NM_000862.3	ENSP00000358421.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251304 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135810

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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	8.2
DANN	Benign	0.96
DEOGEN2	Uncertain	0.59	D;D;D
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.57	T;.;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.8	.;L;L
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Uncertain	0.46
Sift	Benign	0.087	T;D;D
Sift4G	Uncertain	0.030	D;T;T
Polyphen		0.028	.;B;B
Vest4		0.21, 0.19
MVP		0.81
MPC		0.035
ClinPred		0.53	D
GERP RS		-0.39
Varity_R		0.20
gMVP		0.19

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: rs587670461; hg19: chr1-120050160;