11-43680967-C-T

Variant summary

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

The NM_016142.3(HSD17B12):​c.140C>T​(p.Pro47Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000305 in 1,606,124 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: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

HSD17B12
NM_016142.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

Publications

1 publications found
Variant links:
Genes affected
HSD17B12 (HGNC:18646): (hydroxysteroid 17-beta dehydrogenase 12) This gene encodes a very important 17beta-hydroxysteroid dehydrogenase (17beta-HSD) that converts estrone into estradiol in ovarian tissue. This enzyme is also involved in fatty acid elongation. [provided by RefSeq, Oct 2011]

Genome browser will be placed here

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=0.10672659).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HSD17B12NM_016142.3 linkc.140C>T p.Pro47Leu missense_variant Exon 1 of 11 ENST00000278353.10 NP_057226.1 Q53GQ0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HSD17B12ENST00000278353.10 linkc.140C>T p.Pro47Leu missense_variant Exon 1 of 11 1 NM_016142.3 ENSP00000278353.4 Q53GQ0-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
151818
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000589
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000247
AC:
6
AN:
242564
AF XY:
0.0000379
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000553
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000309
AC:
45
AN:
1454186
Hom.:
0
Cov.:
30
AF XY:
0.0000305
AC XY:
22
AN XY:
722332
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33306
American (AMR)
AF:
0.00
AC:
0
AN:
44082
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25806
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39462
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85918
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53080
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5612
European-Non Finnish (NFE)
AF:
0.0000397
AC:
44
AN:
1107006
Other (OTH)
AF:
0.0000167
AC:
1
AN:
59914
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.457
Heterozygous variant carriers
0
3
5
8
10
13
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
AF:
0.0000263
AC:
4
AN:
151938
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74294
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41488
American (AMR)
AF:
0.00
AC:
0
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3466
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5046
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4814
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10578
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000589
AC:
4
AN:
67954
Other (OTH)
AF:
0.00
AC:
0
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
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

Genome 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
Alfa
AF:
0.0000332
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000330
AC:
4
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 08, 2022
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.140C>T (p.P47L) alteration is located in exon 1 (coding exon 1) of the HSD17B12 gene. This alteration results from a C to T substitution at nucleotide position 140, causing the proline (P) at amino acid position 47 to be replaced by a leucine (L). 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
0.11
BayesDel_addAF
Benign
-0.067
T
BayesDel_noAF
Benign
-0.15
CADD
Uncertain
24
DANN
Benign
0.87
DEOGEN2
Uncertain
0.46
T;T;.;T
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.55
D
LIST_S2
Benign
0.78
T;T;T;T
M_CAP
Benign
0.063
D
MetaRNN
Benign
0.11
T;T;T;T
MetaSVM
Benign
-0.43
T
MutationAssessor
Benign
1.7
L;.;L;.
PhyloP100
3.4
PrimateAI
Uncertain
0.48
T
PROVEAN
Uncertain
-2.6
D;N;D;.
REVEL
Uncertain
0.29
Sift
Benign
0.070
T;D;D;.
Sift4G
Benign
0.25
T;T;T;.
Polyphen
0.014
B;.;.;.
Vest4
0.36
MVP
0.63
MPC
0.28
ClinPred
0.18
T
GERP RS
4.5
PromoterAI
0.046
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.11
gMVP
0.89
Mutation Taster
=75/25
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs201719014; hg19: chr11-43702517; API