Variant chr17-29566923-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198147.3(ABHD15):c.44T>C(p.Leu15Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000301 in 1,329,904 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

ABHD15
NM_198147.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

Variant links:

Genes affected

ABHD15 (HGNC:26971): (abhydrolase domain containing 15) Predicted to enable acylglycerol lipase activity and short-chain carboxylesterase activity. Predicted to be involved in cellular lipid metabolic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ABHD15 links:

ABHD15-AS1 (HGNC:49685): (ABHD15 antisense RNA 1)

ABHD15-AS1 links:

TP53I13 (HGNC:25102): (tumor protein p53 inducible protein 13) Involved in several processes, including negative regulation of cell cycle; response to UV; and response to xenobiotic stimulus. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TP53I13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABHD15	NM_198147.3 linkuse as main transcript	c.44T>C	p.Leu15Pro	missense_variant	1/2	ENST00000307201.5
TP53I13	XM_047437003.1 linkuse as main transcript	c.-275+335A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ABHD15	ENST00000307201.5 linkuse as main transcript	c.44T>C	p.Leu15Pro	missense_variant	1/2	1	NM_198147.3	P1
ABHD15-AS1	ENST00000581474.1 linkuse as main transcript	n.153+6224A>G		intron_variant, non_coding_transcript_variant		5
TP53I13	ENST00000578073.1 linkuse as main transcript	n.177+695A>G		intron_variant, non_coding_transcript_variant		4
TP53I13	ENST00000584522.1 linkuse as main transcript	n.288+335A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000262

AC:

AN:

76192

Hom.:

AF XY:

0.0000227

AC XY:

AN XY:

44036

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000301

AC:

AN:

1329904

Hom.:

Cov.:

AF XY:

0.00000152

AC XY:

AN XY:

655794

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000110

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:

9.46e-7

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

Mar 07, 2024

The c.44T>C (p.L15P) alteration is located in exon 1 (coding exon 1) of the ABHD15 gene. This alteration results from a T to C substitution at nucleotide position 44, causing the leucine (L) at amino acid position 15 to be replaced by a proline (P). 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

0.0068

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.57

DEOGEN2

Benign

0.018

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.42

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.65

REVEL

Benign

0.20

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.059

Polyphen

0.68

Vest4

0.68

MutPred

0.38

Gain of catalytic residue at L15 (P = 0.0318);

MVP

0.19

MPC

1.4

ClinPred

0.14

GERP RS

1.6

Varity_R

0.40

gMVP

0.69

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over