Genetic Variant HSD17B13:p.Gln270Lys (chr4-87310247-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_178135.5(HSD17B13):c.808C>A(p.Gln270Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,408,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HSD17B13
NM_178135.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.690

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11871055).

BP6

Variant 4-87310247-G-T is Benign according to our data. Variant chr4-87310247-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2337503.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B13	NM_178135.5 link	c.808C>A	p.Gln270Lys	missense_variant	Exon 6 of 7	ENST00000328546.5	NP_835236.2	Q7Z5P4-1
HSD17B13	NM_001136230.3 link	c.700C>A	p.Gln234Lys	missense_variant	Exon 5 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.808C>A	p.Gln270Lys	missense_variant	Exon 6 of 7	1	NM_178135.5	ENSP00000333300.4		Q7Z5P4-1
HSD17B13	ENST00000302219.10 link	c.700C>A	p.Gln234Lys	missense_variant	Exon 5 of 6	1		ENSP00000305438.6		Q7Z5P4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1408500

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

700294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29430

American (AMR)

AF:

0.00

AC:

AN:

31224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24284

East Asian (EAS)

AF:

0.00

AC:

AN:

36600

South Asian (SAS)

AF:

0.00

AC:

AN:

77812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52650

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5566

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1092926

Other (OTH)

AF:

0.00

AC:

AN:

58008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 19, 2022

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.71

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.0023

.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.28

T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.55

.;N

PhyloP100

0.69

PrimateAI

Benign

0.31

PROVEAN

Benign

0.95

N;N

REVEL

Benign

0.19

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.20

MutPred

0.67

.;Gain of methylation at Q270 (P = 0.0273);

MVP

0.53

MPC

0.13

ClinPred

0.079

GERP RS

-0.022

Varity_R

0.043

gMVP

0.48

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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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4-87310247-G-T

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