Variant 11-43815500-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016142.3(HSD17B12):c.455A>G(p.Asn152Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HSD17B12
NM_016142.3 missense, splice_region

Scores

Splicing: ADA: 0.06070

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.829

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]

HSD17B12 links:

HSD17B12 (HGNC:):

HSD17B12 links:

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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=0.09465623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B12	NM_016142.3 linkuse as main transcript	c.455A>G	p.Asn152Ser	missense_variant, splice_region_variant	5/11	ENST00000278353.10	NP_057226.1	Q53GQ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B12	ENST00000278353.10 linkuse as main transcript	c.455A>G	p.Asn152Ser	missense_variant, splice_region_variant	5/11	1	NM_016142.3	ENSP00000278353.4		Q53GQ0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1401864

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

694530

Gnomad4 AFR exome

AF:

0.00

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2024

The c.455A>G (p.N152S) alteration is located in exon 5 (coding exon 5) of the HSD17B12 gene. This alteration results from a A to G substitution at nucleotide position 455, causing the asparagine (N) at amino acid position 152 to be replaced by a serine (S). 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

0.067

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.21

T;T;T;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.81

T;T;T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.095

T;T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

-0.34

N;.;.;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.99

N;N;.;.

REVEL

Benign

0.14

Sift

Benign

0.37

T;T;.;.

Sift4G

Benign

0.34

T;T;.;.

Polyphen

0.027

B;.;.;.

Vest4

0.094

MutPred

0.40

Loss of methylation at K155 (P = 0.1307);.;.;.;

MVP

0.64

MPC

0.21

ClinPred

0.17

GERP RS

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.028

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.061

dbscSNV1_RF

Benign

0.43

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over