chr1-119513857-T-A

Position:

• chr1-119513857-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000862.3(HSD3B1):​c.334T>A​(p.Cys112Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSD3B1 NM_000862.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.47

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.819

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD3B1	NM_000862.3	c.334T>A	p.Cys112Ser	missense_variant	4/4	ENST00000369413.8	NP_000853.1
HSD3B1	NM_001328615.1	c.334T>A	p.Cys112Ser	missense_variant	4/4		NP_001315544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD3B1	ENST00000369413.8	c.334T>A	p.Cys112Ser	missense_variant	4/4	1	NM_000862.3	ENSP00000358421.3
HSD3B1	ENST00000528909.1	c.334T>A	p.Cys112Ser	missense_variant	3/3	1		ENSP00000432268.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.334T>A (p.C112S) alteration is located in exon 4 (coding exon 3) of the HSD3B1 gene. This alteration results from a T to A substitution at nucleotide position 334, causing the cysteine (C) at amino acid position 112 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.71	D;D
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	.;T
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Uncertain	0.50	D
MutationAssessor	Pathogenic	3.0	M;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-9.4	D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0020	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.52
MVP		0.92
MPC		0.19
ClinPred		1.0	D
GERP RS		2.5
Varity_R		0.82
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-120056480;