rs9938550

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025193.4(HSD3B7):​c.748A>C​(p.Thr250Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/17 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. T250A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Consequence

HSD3B7
NM_025193.4 missense

Scores

16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.602
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.086544305).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HSD3B7NM_025193.4 linkc.748A>C p.Thr250Pro missense_variant Exon 7 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.748A>C p.Thr250Pro missense_variant Exon 7 of 7 1 NM_025193.4 ENSP00000297679.5 Q9H2F3-1
HSD3B7ENST00000262520.10 linkc.585A>C p.Gln195His missense_variant Exon 6 of 6 2 ENSP00000262520.6 Q9H2F3-2
ENSG00000279196ENST00000624286.1 linkn.450T>G non_coding_transcript_exon_variant Exon 1 of 1 6

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
61
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.058
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
7.1
DANN
Benign
0.52
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.072
N
LIST_S2
Benign
0.24
T
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.087
T
MetaSVM
Benign
-0.81
T
PROVEAN
Benign
1.2
N
REVEL
Benign
0.099
Sift
Benign
0.26
T
Sift4G
Benign
0.25
T
Vest4
0.042
MutPred
0.49
Loss of solvent accessibility (P = 0.0576);
MVP
0.21
ClinPred
0.027
T
GERP RS
0.28

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs9938550; hg19: chr16-30999142; API