Genetic Variant HSD17B14:p.Glu234Lys (chr19-48813288-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016246.3(HSD17B14):c.700G>A(p.Glu234Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000689 in 1,450,740 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

HSD17B14
NM_016246.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 3.61

Variant links:

Genes affected

HSD17B14 (HGNC:23238): (hydroxysteroid 17-beta dehydrogenase 14) 17-beta-hydroxysteroid dehydrogenases, such as HSD17B14, are primarily involved in metabolism of steroids at the C17 position and also of other substrates, such as fatty acids, prostaglandins, and xenobiotics (Lukacik et al., 2007 [PubMed 17067289]).[supplied by OMIM, Jun 2009]

HSD17B14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B14	NM_016246.3 link	c.700G>A	p.Glu234Lys	missense_variant	Exon 9 of 9	ENST00000263278.9	NP_057330.2	Q9BPX1A0A140VJH8
HSD17B14	XM_005258969.5 link	c.603G>A	p.Pro201Pro	synonymous_variant	Exon 8 of 8		XP_005259026.1
HSD17B14	XM_047438897.1 link	c.*292G>A		downstream_gene_variant			XP_047294853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HSD17B14	ENST00000263278.9 link	c.700G>A	p.Glu234Lys	missense_variant	Exon 9 of 9	1	NM_016246.3	ENSP00000263278.3	Q9BPX1
HSD17B14	ENST00000599157.5 link	c.628G>A	p.Glu210Lys	missense_variant	Exon 8 of 8	3		ENSP00000472746.1	M0R2R3
HSD17B14	ENST00000595764.1 link	c.495G>A	p.Pro165Pro	synonymous_variant	Exon 7 of 7	5		ENSP00000469557.1	M0QY35
HSD17B14	ENST00000596349.5 link	c.285G>A	p.Pro95Pro	synonymous_variant	Exon 4 of 4	5		ENSP00000471631.1	M0R147

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000134

AC:

AN:

224346

Hom.:

AF XY:

0.0000165

AC XY:

AN XY:

121524

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000935

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000689

AC:

AN:

1450740

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

720572

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000698

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.700G>A (p.E234K) alteration is located in exon 9 (coding exon 9) of the HSD17B14 gene. This alteration results from a G to A substitution at nucleotide position 700, causing the glutamic acid (E) at amino acid position 234 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

High myopia

Uncertain:1

Dec 17, 2018

Institute of Human Genetics, Polish Academy of Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0087

T;.

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.051

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.6

D;.

REVEL

Benign

0.23

Sift

Benign

0.077

T;.

Sift4G

Uncertain

0.043

D;D

Polyphen

1.0

D;.

Vest4

0.39

MutPred

0.71

Gain of ubiquitination at E234 (P = 0.0247);.;

MVP

0.50

MPC

0.39

ClinPred

0.94

GERP RS

4.5

Varity_R

0.76

gMVP

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over