rs775304061

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_025193.4(HSD3B7):c.94C>T(p.Arg32Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,605,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R32Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

HSD3B7
NM_025193.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.52

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

congenital bile acid synthesis defect 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

HSD3B7 links:

ENSG00000279196 (HGNC:):

ENSG00000279196 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2690716).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025193.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HSD3B7	NM_025193.4	MANE Select	c.94C>T	p.Arg32Trp	missense	Exon 2 of 7	NP_079469.2
HSD3B7	NM_001142777.2		c.94C>T	p.Arg32Trp	missense	Exon 2 of 6	NP_001136249.1	Q9H2F3-2
HSD3B7	NM_001142778.2		c.94C>T	p.Arg32Trp	missense	Exon 2 of 6	NP_001136250.1	Q9H2F3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HSD3B7	ENST00000297679.10	TSL:1 MANE Select	c.94C>T	p.Arg32Trp	missense	Exon 2 of 7	ENSP00000297679.5	Q9H2F3-1
HSD3B7	ENST00000867909.1		c.94C>T	p.Arg32Trp	missense	Exon 2 of 7	ENSP00000537968.1
HSD3B7	ENST00000867910.1		c.94C>T	p.Arg32Trp	missense	Exon 2 of 7	ENSP00000537969.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD2 exomes

AF:

0.0000216

AC:

AN:

230992

AF XY:

0.0000239

show subpopulations

Gnomad AFR exome

AF:

0.0000707

Gnomad AMR exome

AF:

0.0000608

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000570

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000241

AC:

AN:

1453548

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

722444

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33368

American (AMR)

AF:

0.0000458

AC:

AN:

43646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25874

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39562

South Asian (SAS)

AF:

0.0000590

AC:

AN:

84782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52214

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4496

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

1109630

Other (OTH)

AF:

0.0000834

AC:

AN:

59976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000241

AC:

AN:

41468

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.59

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.055

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.78

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.27

MetaSVM

Uncertain

0.040

MutationAssessor

Pathogenic

3.2

PhyloP100

1.5

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.34

Sift

Benign

0.21

Sift4G

Benign

0.20

Polyphen

0.014

Vest4

0.21

MutPred

0.54

Gain of catalytic residue at L30 (P = 0.0112)

MVP

0.91

MPC

0.29

ClinPred

0.54

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.31

gMVP

0.71

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over