GeneBe

1-119514535-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000862.3(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
NM_000862.3 missense

Scores

1
9
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25

Publications

42 publications found
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]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

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

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
HSD3B1
NM_000862.3
MANE Select
c.1012C>Gp.Leu338Val
missense
Exon 4 of 4NP_000853.1
HSD3B1
NM_001328615.1
c.1012C>Gp.Leu338Val
missense
Exon 4 of 4NP_001315544.1

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
HSD3B1
ENST00000369413.8
TSL:1 MANE Select
c.1012C>Gp.Leu338Val
missense
Exon 4 of 4ENSP00000358421.3
HSD3B1
ENST00000528909.1
TSL:1
c.1012C>Gp.Leu338Val
missense
Exon 3 of 3ENSP00000432268.1
ENSG00000293080
ENST00000632456.2
TSL:6
n.243-24423G>C
intron
N/A

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
151720
Hom.:
0
Cov.:
30
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
African (AFR)
AF:
0.00
AC:
0
AN:
41330
American (AMR)
AF:
0.00
AC:
0
AN:
15210
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3462
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5140
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4808
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10510
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67956
Other (OTH)
AF:
0.00
AC:
0
AN:
2078

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM
Uncertain
0.40
D
MutationAssessor
Pathogenic
3.7
H
PhyloP100
1.3
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-1.9
N
REVEL
Uncertain
0.43
Sift
Uncertain
0.011
D
Sift4G
Uncertain
0.024
D
Polyphen
0.94
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
Mutation Taster
=89/11
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

Publications

Other links and lift over

dbSNP: rs6203; hg19: chr1-120057158; API