chr17-29566822-C-T

Position:

chr17-29566822-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000307201.5(ABHD15):c.145G>A(p.Glu49Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000029 in 1,516,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

ABHD15
ENST00000307201.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061029643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD15	NM_198147.3 linkuse as main transcript	c.145G>A	p.Glu49Lys	missense_variant	1/2	ENST00000307201.5	NP_937790.2
TP53I13	XM_047437003.1 linkuse as main transcript	c.-275+234C>T		intron_variant			XP_047292959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ABHD15	ENST00000307201.5 linkuse as main transcript	c.145G>A	p.Glu49Lys	missense_variant	1/2	1	NM_198147.3	ENSP00000302657	P1
ABHD15-AS1	ENST00000581474.1 linkuse as main transcript	n.153+6123C>T		intron_variant, non_coding_transcript_variant		5
TP53I13	ENST00000578073.1 linkuse as main transcript	n.177+594C>T		intron_variant, non_coding_transcript_variant		4
TP53I13	ENST00000584522.1 linkuse as main transcript	n.288+234C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000546

AC:

AN:

109808

Hom.:

AF XY:

0.0000491

AC XY:

AN XY:

61094

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000884

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000494

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000731

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000293

AC:

AN:

1364530

Hom.:

Cov.:

AF XY:

0.0000223

AC XY:

AN XY:

673274

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000322

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000519

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000196

Gnomad4 OTH exome

AF:

0.0000351

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151928

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000436

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000384

AC:

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

Dec 11, 2023

The c.145G>A (p.E49K) alteration is located in exon 1 (coding exon 1) of the ABHD15 gene. This alteration results from a G to A substitution at nucleotide position 145, causing the glutamic acid (E) at amino acid position 49 to be replaced by a lysine (K). 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

0.089

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0060

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.59

M_CAP

Benign

0.027

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.50

REVEL

Benign

0.089

Sift

Uncertain

0.017

Sift4G

Benign

0.11

Polyphen

0.0010

Vest4

0.23

MutPred

0.23

Gain of ubiquitination at E49 (P = 0.0011);

MVP

0.42

MPC

2.0

ClinPred

0.073

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.097

gMVP

0.52

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