GeneBe

rs2056463300

Variant names:

Variant summary

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

The NM_025193.4(HSD3B7):​c.143C>A​(p.Pro48His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000483 in 1,450,218 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. 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. P48R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

HSD3B7
NM_025193.4 missense

Scores

8
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.89
Variant links:
Genes affected
HSD3B7 (HGNC:18324): (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7) This gene encodes an enzyme which is involved in the initial stages of the synthesis of bile acids from cholesterol and a member of the short-chain dehydrogenase/reductase superfamily. The encoded protein is a membrane-associated endoplasmic reticulum protein which is active against 7-alpha hydrosylated sterol substrates. Mutations in this gene are associated with a congenital bile acid synthesis defect which leads to neonatal cholestasis, a form of progressive liver disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

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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 rank MANE Protein UniProt
HSD3B7NM_025193.4 linkc.143C>A p.Pro48His missense_variant Exon 2 of 7 ENST00000297679.10 NP_079469.2 Q9H2F3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HSD3B7ENST00000297679.10 linkc.143C>A p.Pro48His missense_variant Exon 2 of 7 1 NM_025193.4 ENSP00000297679.5 Q9H2F3-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000483
AC:
7
AN:
1450218
Hom.:
0
Cov.:
33
AF XY:
0.00000694
AC XY:
5
AN XY:
720554
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:
0.00000632
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.024
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
22
DANN
Benign
0.97
DEOGEN2
Uncertain
0.52
.;D;T;.
Eigen
Benign
0.020
Eigen_PC
Benign
0.16
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.64
T;T;T;T
M_CAP
Uncertain
0.24
D
MetaRNN
Uncertain
0.48
T;T;T;T
MetaSVM
Uncertain
-0.038
T
MutationAssessor
Benign
2.0
M;M;.;.
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-1.9
N;N;.;.
REVEL
Uncertain
0.33
Sift
Uncertain
0.0080
D;T;.;.
Sift4G
Benign
0.18
T;T;T;T
Polyphen
0.013
.;B;.;.
Vest4
0.39
MutPred
0.49
Loss of catalytic residue at W49 (P = 0.0948);Loss of catalytic residue at W49 (P = 0.0948);Loss of catalytic residue at W49 (P = 0.0948);Loss of catalytic residue at W49 (P = 0.0948);
MVP
0.86
MPC
0.33
ClinPred
0.76
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.27
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr16-30997122; API