1-119511583-G-T

Variant names:

• chr1-119511583-G-T
• NM_000862.3:c.226G>T

Variant summary

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

The NM_000862.3(HSD3B1):​c.226G>T​(p.Val76Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,862 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V76I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HSD3B1 NM_000862.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.613

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 rank	MANE	Protein	UniProt
HSD3B1	NM_000862.3	c.226G>T	p.Val76Phe	missense_variant	Exon 3 of 4	ENST00000369413.8	NP_000853.1
HSD3B1	NM_001328615.1	c.226G>T	p.Val76Phe	missense_variant	Exon 3 of 4		NP_001315544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD3B1	ENST00000369413.8	c.226G>T	p.Val76Phe	missense_variant	Exon 3 of 4	1	NM_000862.3	ENSP00000358421.3
HSD3B1	ENST00000528909.1	c.226G>T	p.Val76Phe	missense_variant	Exon 2 of 3	1		ENSP00000432268.1
HSD3B1	ENST00000531340.5	c.226G>T	p.Val76Phe	missense_variant	Exon 3 of 3	3		ENSP00000435999.1
HSD3B1	ENST00000492140.1	n.361G>T		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460862 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726828

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	0.075
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.59	D;D;D
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.54	T;.;T
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Uncertain	0.058	D
MutationAssessor	Uncertain	2.5	.;M;M
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Uncertain	0.59
Sift	Benign	0.037	D;D;D
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.65	.;P;P
Vest4		0.51
MVP		0.71
MPC		0.16
ClinPred		0.80	D
GERP RS		-2.6
Varity_R		0.16
gMVP		0.56

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: chr1-120054206;