19-48813288-C-T

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

9
10

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]

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
HSD17B14NM_016246.3 linkc.700G>A p.Glu234Lys missense_variant Exon 9 of 9 ENST00000263278.9 NP_057330.2 Q9BPX1A0A140VJH8
HSD17B14XM_005258969.5 linkc.603G>A p.Pro201Pro synonymous_variant Exon 8 of 8 XP_005259026.1
HSD17B14XM_047438897.1 linkc.*292G>A downstream_gene_variant XP_047294853.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HSD17B14ENST00000263278.9 linkc.700G>A p.Glu234Lys missense_variant Exon 9 of 9 1 NM_016246.3 ENSP00000263278.3 Q9BPX1
HSD17B14ENST00000599157.5 linkc.628G>A p.Glu210Lys missense_variant Exon 8 of 8 3 ENSP00000472746.1 M0R2R3
HSD17B14ENST00000595764.1 linkc.495G>A p.Pro165Pro synonymous_variant Exon 7 of 7 5 ENSP00000469557.1 M0QY35
HSD17B14ENST00000596349.5 linkc.285G>A p.Pro95Pro synonymous_variant Exon 4 of 4 5 ENSP00000471631.1 M0R147

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000134
AC:
3
AN:
224346
Hom.:
0
AF XY:
0.0000165
AC XY:
2
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:
10
AN:
1450740
Hom.:
0
Cov.:
32
AF XY:
0.00000555
AC XY:
4
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.:
32
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
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0087
T;.
Eigen
Uncertain
0.25
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.051
D
MetaRNN
Uncertain
0.44
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;.
PrimateAI
Uncertain
0.73
T
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
D
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.

Other links and lift over

dbSNP: rs1400589983; hg19: chr19-49316545; COSMIC: COSV99622656; COSMIC: COSV99622656; API