NM_178135.5:c.556T>G

Variant names:

Variant summary

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

The NM_178135.5(HSD17B13):c.556T>G(p.Cys186Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000318 in 1,570,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HSD17B13
NM_178135.5 missense, splice_region

Scores

Splicing: ADA: 0.08821

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

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:

Genome browser will be placed here

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, 0.91

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B13	NM_178135.5 link	c.556T>G	p.Cys186Gly	missense_variant, splice_region_variant	Exon 4 of 7	ENST00000328546.5	NP_835236.2	Q7Z5P4-1
HSD17B13	NM_001136230.3 link	c.448T>G	p.Cys150Gly	missense_variant, splice_region_variant	Exon 3 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.556T>G	p.Cys186Gly	missense_variant, splice_region_variant	Exon 4 of 7	1	NM_178135.5	ENSP00000333300.4		Q7Z5P4-1
HSD17B13	ENST00000302219.10 link	c.448T>G	p.Cys150Gly	missense_variant, splice_region_variant	Exon 3 of 6	1		ENSP00000305438.6		Q7Z5P4-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00000403

AC:

AN:

248040

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000211

AC:

AN:

1418630

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

706912

show subpopulations

African (AFR)

AF:

0.0000615

AC:

AN:

32534

American (AMR)

AF:

0.00

AC:

AN:

43734

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25732

East Asian (EAS)

AF:

0.00

AC:

AN:

39340

South Asian (SAS)

AF:

0.00

AC:

AN:

84642

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53254

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074856

Other (OTH)

AF:

0.0000170

AC:

AN:

58876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 28, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.556T>G (p.C186G) alteration is located in exon 4 (coding exon 4) of the HSD17B13 gene. This alteration results from a T to G substitution at nucleotide position 556, causing the cysteine (C) at amino acid position 186 to be replaced by a glycine (G). 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

Uncertain

0.50

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.38

.;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D

M_CAP

Uncertain

0.21

MetaRNN

Pathogenic

0.91

D;D

MetaSVM

Uncertain

0.51

MutationAssessor

Benign

1.3

.;L

PhyloP100

2.4

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-9.4

D;D

REVEL

Uncertain

0.63

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.99

D;D

Vest4

0.82

MutPred

0.72

.;Loss of stability (P = 0.0465);

MVP

0.95

MPC

0.58

ClinPred

0.99

GERP RS

5.2

Varity_R

0.87

gMVP

0.48

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.088

dbscSNV1_RF

Benign

0.47

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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NM_178135.5:c.556T>G

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