rs144261994

Variant names:

• chr1-119507587-G-C
• rs144261994
• NM_000862.3:c.111G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-119507587-G-C
• chr1-119507587-G-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000862.3(HSD3B1):​c.111G>C​(p.Lys37Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000356 in 1,613,880 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 0.00033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (0 hom.)
• Consequence: HSD3B1 NM_000862.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03
• Publications: 3 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.028333008).

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.111G>C	p.Lys37Asn	missense	Exon 2 of 4	NP_000853.1	P14060
	HSD3B1	NM_001328615.1		c.111G>C	p.Lys37Asn	missense	Exon 2 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.111G>C	p.Lys37Asn	missense	Exon 2 of 4	ENSP00000358421.3	P14060
	HSD3B1	ENST00000528909.1	TSL:1	c.111G>C	p.Lys37Asn	missense	Exon 1 of 3	ENSP00000432268.1	P14060
	HSD3B1	ENST00000531340.5	TSL:3	c.111G>C	p.Lys37Asn	missense	Exon 2 of 3	ENSP00000435999.1	E9PRN7

Frequencies

GnomAD3 genomes AF: 0.000329 AC: 50 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000485 AC: 122 AN: 251400 AF XY: 0.000530

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00466

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000255

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000359 AC: 525 AN: 1461734 Hom.: 0 Cov.: 31 AF XY: 0.000342 AC XY: 249 AN XY: 727178

African (AFR) AF: 0.0000896 AC: 3 AN: 33468

American (AMR) AF: 0.00119 AC: 53 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00425 AC: 111 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.000277 AC: 308 AN: 1111898

Other (OTH) AF: 0.000696 AC: 42 AN: 60382

GnomAD4 genome AF: 0.000329 AC: 50 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.000377 AC XY: 28 AN XY: 74326

African (AFR) AF: 0.0000724 AC: 3 AN: 41444

American (AMR) AF: 0.000851 AC: 13 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68026

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.000771 Hom.: 0

Bravo AF: 0.000397

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000395 AC: 48

EpiCase AF: 0.000491

EpiControl AF: 0.000593

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	Pathogenic	0.63
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	-0.070
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.028	T
MetaSVM	Uncertain	-0.063	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.0
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.39
Sift	Benign	0.069	T
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.51
MVP		0.84
MPC		0.070
ClinPred		0.12	T
GERP RS		-1.1
PromoterAI		-0.0090	Neutral
Varity_R		0.22
gMVP		0.23
Mutation Taster		=75/25	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: rs144261994; hg19: chr1-120050210; COSMIC: COSV106087087;