16-30985761-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1

The NM_025193.4(HSD3B7):c.103C>G(p.Arg35Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000494 in 1,604,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R35W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

HSD3B7
NM_025193.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -0.0620

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]

HSD3B7 links:

ENSG00000279196 (HGNC:):

ENSG00000279196 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009693742).

BP6

Variant 16-30985761-C-G is Benign according to our data. Variant chr16-30985761-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 195382.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=2}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00262 (399/152346) while in subpopulation AFR AF= 0.00883 (367/41578). AF 95% confidence interval is 0.00808. There are 0 homozygotes in gnomad4. There are 197 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD3B7	NM_025193.4 link	c.103C>G	p.Arg35Gly	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
HSD3B7	ENST00000297679.10 link	c.103C>G	p.Arg35Gly	missense_variant	Exon 2 of 7	1	NM_025193.4	ENSP00000297679.5		Q9H2F3-1

Frequencies

GnomAD3 genomes

AF:

0.00259

AC:

394

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00873

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000654

AC:

150

AN:

229224

Hom.:

AF XY:

0.000505

AC XY:

AN XY:

124762

show subpopulations

Gnomad AFR exome

AF:

0.00897

Gnomad AMR exome

AF:

0.000399

Gnomad ASJ exome

AF:

0.000629

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000293

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000271

AC:

394

AN:

1452576

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

175

AN XY:

721902

show subpopulations

Gnomad4 AFR exome

AF:

0.00920

Gnomad4 AMR exome

AF:

0.000554

Gnomad4 ASJ exome

AF:

0.000309

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000945

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000684

GnomAD4 genome

AF:

0.00262

AC:

399

AN:

152346

Hom.:

Cov.:

AF XY:

0.00264

AC XY:

197

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00883

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000228

Hom.:

Bravo

AF:

0.00301

ESP6500AA

AF:

0.00661

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000767

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Jan 09, 2023

Mayo Clinic Laboratories, Mayo Clinic

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BS1 -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

HSD3B7: BS1 -

not specified

Benign:1

Nov 24, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.46

.;T;T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.67

T;T;T;T

MetaRNN

Benign

0.0097

T;T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.0

L;L;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.5

N;N;.;.

REVEL

Uncertain

0.33

Sift

Benign

0.29

T;T;.;.

Sift4G

Benign

0.38

T;T;T;T

Polyphen

0.54

.;P;.;.

Vest4

0.26

MVP

0.81

MPC

0.45

ClinPred

0.0097

GERP RS

2.8

Varity_R

0.10

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over