chr1-119514535-C-G

Position:

• chr1-119514535-C-G

Variant summary

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

The ENST00000369413.8(HSD3B1):​c.1012C>G​(p.Leu338Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: HSD3B1 ENST00000369413.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD3B1	NM_000862.3	c.1012C>G	p.Leu338Val	missense_variant	4/4	ENST00000369413.8	NP_000853.1
HSD3B1	NM_001328615.1	c.1012C>G	p.Leu338Val	missense_variant	4/4		NP_001315544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD3B1	ENST00000369413.8	c.1012C>G	p.Leu338Val	missense_variant	4/4	1	NM_000862.3	ENSP00000358421	P1
HSD3B1	ENST00000528909.1	c.1012C>G	p.Leu338Val	missense_variant	3/3	1		ENSP00000432268	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151720 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 66

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 151720 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74058

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;T
Eigen	Benign	0.17
Eigen_PC	Benign	-0.016
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.88	.;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Pathogenic	3.7	H;H
MutationTaster	Benign	0.56	N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.9	N;N
REVEL	Uncertain	0.43
Sift	Uncertain	0.011	D;D
Sift4G	Uncertain	0.024	D;D
Polyphen		0.94	P;P
Vest4		0.29
MVP		0.86
MPC		0.15
ClinPred		0.93	D
GERP RS		1.3
Varity_R		0.15
gMVP		0.32

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: rs6203; hg19: chr1-120057158;