Variant 13-108229511-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000375898.4(ABHD13):c.293G>A(p.Arg98His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000572 in 1,613,362 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 1 hom. )

Consequence

ABHD13
ENST00000375898.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

Variant links:

Genes affected

ABHD13 (HGNC:20293): (abhydrolase domain containing 13) Predicted to enable palmitoyl-(protein) hydrolase activity. Predicted to be involved in protein depalmitoylation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ABHD13 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=0.044600546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD13	NM_032859.3 linkuse as main transcript	c.293G>A	p.Arg98His	missense_variant	2/2	ENST00000375898.4	NP_116248.2
ABHD13	XM_011521128.4 linkuse as main transcript	c.293G>A	p.Arg98His	missense_variant	2/2		XP_011519430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD13	ENST00000375898.4 linkuse as main transcript	c.293G>A	p.Arg98His	missense_variant	2/2	1	NM_032859.3	ENSP00000365063	P1

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000722

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000736

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000498

AC:

125

AN:

250828

Hom.:

AF XY:

0.000524

AC XY:

AN XY:

135576

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000883

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000585

AC:

855

AN:

1461374

Hom.:

Cov.:

AF XY:

0.000571

AC XY:

415

AN XY:

726984

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.000694

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.000447

AC:

AN:

151988

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000722

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000736

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000636

Hom.:

Bravo

AF:

0.000397

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.000593

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000296

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

Aug 10, 2021

The c.293G>A (p.R98H) alteration is located in exon 2 (coding exon 1) of the ABHD13 gene. This alteration results from a G to A substitution at nucleotide position 293, causing the arginine (R) at amino acid position 98 to be replaced by a histidine (H). 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

-0.45

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

Eigen

Benign

0.023

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.63

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0068

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.95

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.063

Sift

Benign

0.14

Sift4G

Benign

0.085

Polyphen

0.0040

Vest4

0.058

MVP

0.52

MPC

0.34

ClinPred

0.019

GERP RS

5.0

Varity_R

0.084

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