4-87310247-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178135.5(HSD17B13):​c.808C>G​(p.Gln270Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q270K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

HSD17B13
NM_178135.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.690

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]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07816246).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HSD17B13NM_178135.5 linkc.808C>G p.Gln270Glu missense_variant Exon 6 of 7 ENST00000328546.5 NP_835236.2 Q7Z5P4-1
HSD17B13NM_001136230.3 linkc.700C>G p.Gln234Glu missense_variant Exon 5 of 6 NP_001129702.1 Q7Z5P4-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HSD17B13ENST00000328546.5 linkc.808C>G p.Gln270Glu missense_variant Exon 6 of 7 1 NM_178135.5 ENSP00000333300.4 Q7Z5P4-1
HSD17B13ENST00000302219.10 linkc.700C>G p.Gln234Glu missense_variant Exon 5 of 6 1 ENSP00000305438.6 Q7Z5P4-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.10e-7
AC:
1
AN:
1408500
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
700294
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
29430
American (AMR)
AF:
0.00
AC:
0
AN:
31224
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24284
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36600
South Asian (SAS)
AF:
0.00
AC:
0
AN:
77812
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52650
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5566
European-Non Finnish (NFE)
AF:
9.15e-7
AC:
1
AN:
1092926
Other (OTH)
AF:
0.00
AC:
0
AN:
58008
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
0.11
DANN
Benign
0.14
DEOGEN2
Benign
0.0050
.;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.00041
N
LIST_S2
Benign
0.29
T;T
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.078
T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
-1.8
.;N
PhyloP100
0.69
PrimateAI
Benign
0.28
T
PROVEAN
Benign
0.73
N;N
REVEL
Benign
0.14
Sift
Benign
0.77
T;T
Sift4G
Benign
0.61
T;T
Polyphen
0.0
B;B
Vest4
0.19
MutPred
0.58
.;Loss of glycosylation at P274 (P = 0.0515);
MVP
0.55
MPC
0.11
ClinPred
0.085
T
GERP RS
-0.022
Varity_R
0.031
gMVP
0.32
Mutation Taster
=98/2
polymorphism

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

Other links and lift over

dbSNP: rs1734500710; hg19: chr4-88231399; API