11-43815500-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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

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]

ACMG classification

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	UniProt
HSD17B12	NM_016142.3	c.455A>G	p.Asn152Ser	missense_variant, splice_region_variant	5/11	ENST00000278353.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B12	ENST00000278353.10	c.455A>G	p.Asn152Ser	missense_variant, splice_region_variant	5/11	1	NM_016142.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1401864 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	12
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	D
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.095	T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	-0.34	N;.;.;.
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.41	T
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	T
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.

Other links and lift over

hg19: chr11-43837050;