Genetic Variant HSD17B13:p.Pro260Ser (chr4-87310277-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_178135.5(HSD17B13):c.778C>T(p.Pro260Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0572 in 1,579,316 control chromosomes in the GnomAD database, including 2,998 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P260Q) has been classified as Benign.

Frequency

Genomes: 𝑓 0.044 ( 214 hom., cov: 32)

Exomes 𝑓: 0.059 ( 2784 hom. )

Consequence

HSD17B13
NM_178135.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.12

Publications

44 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046227574).

BP6

Variant 4-87310277-G-A is Benign according to our data. Variant chr4-87310277-G-A is described in ClinVar as [Benign]. Clinvar id is 1273874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B13	NM_178135.5 link	c.778C>T	p.Pro260Ser	missense_variant	Exon 6 of 7	ENST00000328546.5	NP_835236.2	Q7Z5P4-1
HSD17B13	NM_001136230.3 link	c.670C>T	p.Pro224Ser	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.778C>T	p.Pro260Ser	missense_variant	Exon 6 of 7	1	NM_178135.5	ENSP00000333300.4		Q7Z5P4-1
HSD17B13	ENST00000302219.10 link	c.670C>T	p.Pro224Ser	missense_variant	Exon 5 of 6	1		ENSP00000305438.6		Q7Z5P4-2

Frequencies

GnomAD3 genomes

AF:

0.0445

AC:

6764

AN:

151902

Hom.:

213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.0483

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0245

Gnomad FIN

AF:

0.0512

Gnomad MID

AF:

0.0414

Gnomad NFE

AF:

0.0619

Gnomad OTH

AF:

0.0532

GnomAD2 exomes

AF:

0.0473

AC:

10244

AN:

216760

AF XY:

0.0492

show subpopulations

Gnomad AFR exome

AF:

0.00966

Gnomad AMR exome

AF:

0.0261

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0560

Gnomad NFE exome

AF:

0.0615

Gnomad OTH exome

AF:

0.0560

GnomAD4 exome

AF:

0.0586

AC:

83580

AN:

1427306

Hom.:

2784

Cov.:

AF XY:

0.0580

AC XY:

41160

AN XY:

709590

show subpopulations

African (AFR)

AF:

0.00806

AC:

248

AN:

30766

American (AMR)

AF:

0.0290

AC:

1084

AN:

37350

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

3135

AN:

25234

East Asian (EAS)

AF:

0.0000537

AC:

AN:

37228

South Asian (SAS)

AF:

0.0263

AC:

2103

AN:

79930

European-Finnish (FIN)

AF:

0.0567

AC:

3004

AN:

53014

Middle Eastern (MID)

AF:

0.0477

AC:

270

AN:

5666

European-Non Finnish (NFE)

AF:

0.0638

AC:

70095

AN:

1099180

Other (OTH)

AF:

0.0617

AC:

3639

AN:

58938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

4320

8640

12961

17281

21601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0445

AC:

6762

AN:

152010

Hom.:

214

Cov.:

AF XY:

0.0433

AC XY:

3219

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0114

AC:

472

AN:

41440

American (AMR)

AF:

0.0482

AC:

736

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

448

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.0251

AC:

121

AN:

4814

European-Finnish (FIN)

AF:

0.0512

AC:

539

AN:

10520

Middle Eastern (MID)

AF:

0.0377

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0619

AC:

4209

AN:

67990

Other (OTH)

AF:

0.0531

AC:

112

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

320

640

959

1279

1599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0570

Hom.:

408

Bravo

AF:

0.0445

TwinsUK

AF:

0.0623

AC:

231

ALSPAC

AF:

0.0592

AC:

228

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.0665

AC:

572

ExAC

AF:

0.0475

AC:

5767

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 29, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 30415504) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

.;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

D;D

MetaRNN

Benign

0.0046

T;T

MetaSVM

Uncertain

-0.076

MutationAssessor

Pathogenic

2.9

.;M

PhyloP100

6.1

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-7.3

D;D

REVEL

Uncertain

0.49

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;D

Vest4

0.51

MPC

0.50

ClinPred

0.030

GERP RS

5.1

Varity_R

0.71

gMVP

0.66

Mutation Taster

=94/6

polymorphism (auto)

(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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chr4-87310277-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over