19-48831703-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016246.3(HSD17B14):​c.334G>A​(p.Glu112Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HSD17B14
NM_016246.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.44
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3376766).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HSD17B14NM_016246.3 linkc.334G>A p.Glu112Lys missense_variant Exon 5 of 9 ENST00000263278.9 NP_057330.2 Q9BPX1A0A140VJH8
HSD17B14XM_005258969.5 linkc.334G>A p.Glu112Lys missense_variant Exon 5 of 8 XP_005259026.1
HSD17B14XM_047438897.1 linkc.277+963G>A intron_variant Intron 4 of 6 XP_047294853.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HSD17B14ENST00000263278.9 linkc.334G>A p.Glu112Lys missense_variant Exon 5 of 9 1 NM_016246.3 ENSP00000263278.3 Q9BPX1
HSD17B14ENST00000595764.1 linkc.226G>A p.Glu76Lys missense_variant Exon 4 of 7 5 ENSP00000469557.1 M0QY35
HSD17B14ENST00000599157.5 linkc.297+963G>A intron_variant Intron 4 of 7 3 ENSP00000472746.1 M0R2R3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461758
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727180
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 17, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.334G>A (p.E112K) alteration is located in exon 5 (coding exon 5) of the HSD17B14 gene. This alteration results from a G to A substitution at nucleotide position 334, causing the glutamic acid (E) at amino acid position 112 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
Uncertain
0.42
BayesDel_addAF
Uncertain
0.049
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.015
T;T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.73
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.34
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
L;.
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-1.4
N;.
REVEL
Benign
0.12
Sift
Benign
0.30
T;.
Sift4G
Benign
0.69
T;T
Polyphen
0.63
P;.
Vest4
0.71
MutPred
0.65
Gain of MoRF binding (P = 0.0311);.;
MVP
0.73
MPC
0.31
ClinPred
0.58
D
GERP RS
3.2
Varity_R
0.51
gMVP
0.72

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: rs2035338361; hg19: chr19-49334960; API