rs145376537

Variant names:

• chr1-119514055-G-A
• rs145376537
• NM_000862.3:c.532G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-119514055-G-A
• chr1-119514055-G-C
• chr1-119514055-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000862.3(HSD3B1):​c.532G>A​(p.Gly178Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000115 in 1,613,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: HSD3B1 NM_000862.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.47
• Publications: 2 publications found

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]

ENSG00000293080 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.121313065).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000862.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD3B1	NM_000862.3	MANE Select	c.532G>A	p.Gly178Ser	missense	Exon 4 of 4	NP_000853.1	P14060
	HSD3B1	NM_001328615.1		c.532G>A	p.Gly178Ser	missense	Exon 4 of 4	NP_001315544.1	P14060

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD3B1	ENST00000369413.8	TSL:1 MANE Select	c.532G>A	p.Gly178Ser	missense	Exon 4 of 4	ENSP00000358421.3	P14060
	HSD3B1	ENST00000528909.1	TSL:1	c.532G>A	p.Gly178Ser	missense	Exon 3 of 3	ENSP00000432268.1	P14060
	ENSG00000293080	ENST00000632456.2	TSL:6	n.243-23943C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152096 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000123 AC: 31 AN: 251174 AF XY: 0.0000958

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000118 AC: 173 AN: 1461822 Hom.: 0 Cov.: 31 AF XY: 0.000114 AC XY: 83 AN XY: 727208

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39680

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000141 AC: 157 AN: 1111982

Other (OTH) AF: 0.000116 AC: 7 AN: 60392

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152096 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74298

African (AFR) AF: 0.0000241 AC: 1 AN: 41410

American (AMR) AF: 0.000131 AC: 2 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000755 Hom.: 0

Bravo AF: 0.000110

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.66	D
Eigen	Benign	0.055
Eigen_PC	Benign	-0.010
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.12	T
MetaSVM	Uncertain	-0.0033	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.5
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.46
Sift	Benign	0.043	D
Sift4G	Benign	0.13	T
Polyphen		0.69	P
Vest4		0.11
MVP		0.86
MPC		0.051
ClinPred		0.22	T
GERP RS		2.8
Varity_R		0.45
gMVP		0.68
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

dbSNP: rs145376537; hg19: chr1-120056678;