19-48834332-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016246.3(HSD17B14):​c.154G>A​(p.Glu52Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

HSD17B14
NM_016246.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.428
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23467907).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HSD17B14NM_016246.3 linkc.154G>A p.Glu52Lys missense_variant Exon 3 of 9 ENST00000263278.9 NP_057330.2 Q9BPX1A0A140VJH8
HSD17B14XM_005258969.5 linkc.154G>A p.Glu52Lys missense_variant Exon 3 of 8 XP_005259026.1
HSD17B14XM_047438897.1 linkc.154G>A p.Glu52Lys missense_variant Exon 3 of 7 XP_047294853.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HSD17B14ENST00000263278.9 linkc.154G>A p.Glu52Lys missense_variant Exon 3 of 9 1 NM_016246.3 ENSP00000263278.3 Q9BPX1
HSD17B14ENST00000599157.5 linkc.154G>A p.Glu52Lys missense_variant Exon 3 of 8 3 ENSP00000472746.1 M0R2R3
HSD17B14ENST00000595764.1 linkc.46G>A p.Glu16Lys missense_variant Exon 2 of 7 5 ENSP00000469557.1 M0QY35

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152244
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251104
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135742
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
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:
0.00000479
AC:
7
AN:
1461510
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
727106
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152244
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 10, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.154G>A (p.E52K) alteration is located in exon 3 (coding exon 3) of the HSD17B14 gene. This alteration results from a G to A substitution at nucleotide position 154, causing the glutamic acid (E) at amino acid position 52 to be replaced by a lysine (K). 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
Benign
0.22
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.019
T;.;T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.64
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.84
T;D;T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.23
T;T;T
MetaSVM
Uncertain
-0.14
T
MutationAssessor
Benign
1.7
L;.;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-2.1
N;.;.
REVEL
Uncertain
0.32
Sift
Benign
0.21
T;.;.
Sift4G
Benign
0.17
T;T;T
Polyphen
0.57
P;.;.
Vest4
0.42
MutPred
0.59
Gain of ubiquitination at E52 (P = 0.0211);Gain of ubiquitination at E52 (P = 0.0211);.;
MVP
0.75
MPC
0.34
ClinPred
0.36
T
GERP RS
0.11
Varity_R
0.45
gMVP
0.60

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: rs774784680; hg19: chr19-49337589; API