dbSNP rs866695150: HSD17B13:p.Ala191Val (chr4-87313946-G-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_178135.5(HSD17B13):c.572C>T(p.Ala191Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000283 in 1,411,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

HSD17B13
NM_178135.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.24

Publications

0 publications found

Variant links:

Genes affected

HSD17B13 (HGNC:18685): (hydroxysteroid 17-beta dehydrogenase 13) Predicted to enable oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor and steroid dehydrogenase activity. Acts upstream of or within positive regulation of lipid biosynthetic process. Located in lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

HSD17B13 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.888

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B13	NM_178135.5 link	c.572C>T	p.Ala191Val	missense_variant	Exon 5 of 7	ENST00000328546.5	NP_835236.2	Q7Z5P4-1
HSD17B13	NM_001136230.3 link	c.464C>T	p.Ala155Val	missense_variant	Exon 4 of 6		NP_001129702.1	Q7Z5P4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B13	ENST00000328546.5 link	c.572C>T	p.Ala191Val	missense_variant	Exon 5 of 7	1	NM_178135.5	ENSP00000333300.4		Q7Z5P4-1
HSD17B13	ENST00000302219.10 link	c.464C>T	p.Ala155Val	missense_variant	Exon 4 of 6	1		ENSP00000305438.6		Q7Z5P4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000283

AC:

AN:

1411790

Hom.:

Cov.:

AF XY:

0.00000427

AC XY:

AN XY:

701790

show subpopulations

African (AFR)

AF:

0.000100

AC:

AN:

30004

American (AMR)

AF:

0.00

AC:

AN:

37230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24462

East Asian (EAS)

AF:

0.00

AC:

AN:

36592

South Asian (SAS)

AF:

0.00

AC:

AN:

79356

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5554

European-Non Finnish (NFE)

AF:

9.19e-7

AC:

AN:

1088648

Other (OTH)

AF:

0.00

AC:

AN:

57798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 16, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.572C>T (p.A191V) alteration is located in exon 5 (coding exon 5) of the HSD17B13 gene. This alteration results from a C to T substitution at nucleotide position 572, causing the alanine (A) at amino acid position 191 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.66

.;D

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.84

T;T

M_CAP

Uncertain

0.28

MetaRNN

Pathogenic

0.89

D;D

MetaSVM

Pathogenic

0.93

MutationAssessor

Pathogenic

4.1

.;H

PhyloP100

5.2

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.7

D;D

REVEL

Pathogenic

0.75

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;D

Vest4

0.70

MutPred

0.73

.;Loss of ubiquitination at K189 (P = 0.0768);

MVP

0.99

MPC

0.36

ClinPred

0.99

GERP RS

3.8

Varity_R

0.27

gMVP

0.74

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs866695150

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over