1-119511661-G-A

Variant summary

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

The NM_000862.3(HSD3B1):​c.304G>A​(p.Val102Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,500 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HSD3B1
NM_000862.3 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
HSD3B1NM_000862.3 linkuse as main transcriptc.304G>A p.Val102Met missense_variant 3/4 ENST00000369413.8 NP_000853.1 P14060
HSD3B1NM_001328615.1 linkuse as main transcriptc.304G>A p.Val102Met missense_variant 3/4 NP_001315544.1 P14060

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HSD3B1ENST00000369413.8 linkuse as main transcriptc.304G>A p.Val102Met missense_variant 3/41 NM_000862.3 ENSP00000358421.3 P14060
HSD3B1ENST00000528909.1 linkuse as main transcriptc.304G>A p.Val102Met missense_variant 2/31 ENSP00000432268.1 P14060
HSD3B1ENST00000492140.1 linkuse as main transcriptn.439G>A non_coding_transcript_exon_variant 3/32

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152158
Hom.:
0
Cov.:
31
show subpopulations
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461342
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726984
show subpopulations
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152158
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74328
show subpopulations
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:
0.0000441
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 30, 2024The c.304G>A (p.V102M) alteration is located in exon 3 (coding exon 2) of the HSD3B1 gene. This alteration results from a G to A substitution at nucleotide position 304, causing the valine (V) at amino acid position 102 to be replaced by a methionine (M). 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
0.28
BayesDel_addAF
Uncertain
0.019
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.70
D;D
Eigen
Benign
0.014
Eigen_PC
Benign
-0.26
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.81
.;T
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.53
D;D
MetaSVM
Uncertain
0.68
D
MutationAssessor
Pathogenic
3.4
M;M
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-2.0
N;N
REVEL
Uncertain
0.46
Sift
Uncertain
0.0060
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
0.96
D;D
Vest4
0.34
MVP
0.75
MPC
0.20
ClinPred
0.95
D
GERP RS
-0.66
Varity_R
0.32
gMVP
0.41

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs934558013; hg19: chr1-120054284; API