rs1047303

chr1-119514623-C-Achr1-119514623-C-Gchr1-119514623-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000862.3(HSD3B1):c.1100C>A(p.Thr367Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 1,613,074 control chromosomes in the GnomAD database, including 412,097 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.76 (44941 hom., cov: 29)
  • Exomes 𝑓: 0.71 (367156 hom.)
• Consequence: HSD3B1 NM_000862.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.311

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1095348E-6).
• BP6: Variant 1-119514623-C-A is Benign according to our data. Variant chr1-119514623-C-A is described in ClinVar as [Benign]. Clinvar id is 1274004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD3B1	NM_000862.3	c.1100C>A	p.Thr367Asn	missense_variant	4/4	ENST00000369413.8
HSD3B1	NM_001328615.1	c.1100C>A	p.Thr367Asn	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD3B1	ENST00000369413.8	c.1100C>A	p.Thr367Asn	missense_variant	4/4	1	NM_000862.3	P1
HSD3B1	ENST00000528909.1	c.1100C>A	p.Thr367Asn	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes AF: 0.764 AC: 115773 AN: 151570 Hom.: 44897 Cov.: 29

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.727

GnomAD3 exomes AF: 0.755 AC: 188429 AN: 249654 Hom.: 72300 AF XY: 0.748 AC XY: 100974 AN XY: 134938

Gnomad AFR exome AF: 0.892

Gnomad AMR exome AF: 0.850

Gnomad ASJ exome AF: 0.666

Gnomad EAS exome AF: 0.937

Gnomad SAS exome AF: 0.810

Gnomad FIN exome AF: 0.741

Gnomad NFE exome AF: 0.674

Gnomad OTH exome AF: 0.718

GnomAD4 exome AF: 0.705 AC: 1030890 AN: 1461386 Hom.: 367156 Cov.: 61 AF XY: 0.707 AC XY: 513679 AN XY: 726994

Gnomad4 AFR exome AF: 0.895

Gnomad4 AMR exome AF: 0.840

Gnomad4 ASJ exome AF: 0.670

Gnomad4 EAS exome AF: 0.939

Gnomad4 SAS exome AF: 0.808

Gnomad4 FIN exome AF: 0.742

Gnomad4 NFE exome AF: 0.677

Gnomad4 OTH exome AF: 0.718

GnomAD4 genome AF: 0.764 AC: 115875 AN: 151688 Hom.: 44941 Cov.: 29 AF XY: 0.771 AC XY: 57102 AN XY: 74092

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.924

Gnomad4 SAS AF: 0.825

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.731

Alfa AF: 0.709 Hom.: 16729

Bravo AF: 0.771

TwinsUK AF: 0.675 AC: 2504

ALSPAC AF: 0.671 AC: 2585

ESP6500AA AF: 0.881 AC: 3879

ESP6500EA AF: 0.682 AC: 5860

ExAC AF: 0.755 AC: 91615

Asia WGS AF: 0.866 AC: 3011 AN: 3478

EpiCase AF: 0.657

EpiControl AF: 0.659

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 14, 2020

This variant is associated with the following publications: (PMID: 31932420) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	0.078
Dann	Benign	0.26
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.023	N
MetaRNN	Benign	0.0000011	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.13
Sift	Benign	0.30	T;T
Sift4G	Benign	0.30	T;T
Polyphen		0.021	B;B
Vest4		0.093
MPC		0.029
ClinPred		0.0099	T
GERP RS		-0.043
Varity_R		0.046
gMVP		0.42

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: rs1047303; hg19: chr1-120057246; COSMIC: COSV52489946; COSMIC: COSV52489946;