Variant 3-111991633-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000273359.8(ABHD10):c.833A>T(p.Asp278Val) variant causes a missense change. The variant allele was found at a frequency of 0.00192 in 1,614,118 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 3 hom. )

Consequence

ABHD10
ENST00000273359.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.90

Variant links:

Genes affected

ABHD10 (HGNC:25656): (abhydrolase domain containing 10, depalmitoylase) This gene encodes a mitochondrially-localized enzyme that acts in liver cells as a hydrolase. The encoded protein removes glucuronide from mycophenolic acid acyl-glucuronide. There is a pseudogene for this gene on chromosome 6. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

ABHD10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02749303).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ABHD10	NM_018394.4 linkuse as main transcript	c.833A>T	p.Asp278Val	missense_variant	5/5	ENST00000273359.8	NP_060864.1
ABHD10	NM_001272069.2 linkuse as main transcript	c.*267A>T		3_prime_UTR_variant	6/6		NP_001258998.1
ABHD10	NR_073570.2 linkuse as main transcript	n.685A>T		non_coding_transcript_exon_variant	4/4
ABHD10	NR_073571.2 linkuse as main transcript	n.573A>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD10	ENST00000273359.8 linkuse as main transcript	c.833A>T	p.Asp278Val	missense_variant	5/5	1	NM_018394.4	ENSP00000273359	P1	Q9NUJ1-1
ABHD10	ENST00000491580.1 linkuse as main transcript	c.*421A>T		3_prime_UTR_variant, NMD_transcript_variant	4/4	2		ENSP00000418162
ABHD10	ENST00000493784.1 linkuse as main transcript	c.*378A>T		3_prime_UTR_variant, NMD_transcript_variant	3/3	3		ENSP00000417880

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

224

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00232

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00135

AC:

340

AN:

251354

Hom.:

AF XY:

0.00130

AC XY:

176

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.00233

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00197

AC:

2879

AN:

1461782

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

1362

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.000505

Gnomad4 NFE exome

AF:

0.00238

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.00147

AC:

224

AN:

152336

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

104

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00232

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00173

Hom.:

Bravo

AF:

0.00153

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.00137

AC:

167

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00218

EpiControl

AF:

0.00213

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 26, 2022

The c.833A>T (p.D278V) alteration is located in exon 5 (coding exon 5) of the ABHD10 gene. This alteration results from a A to T substitution at nucleotide position 833, causing the aspartic acid (D) at amino acid position 278 to be replaced by a valine (V). 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

0.34

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.072

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.38

MutationAssessor

Pathogenic

3.4

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-5.5

REVEL

Uncertain

0.38

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0020

Polyphen

0.99

Vest4

0.35

MVP

0.83

MPC

0.66

ClinPred

0.087

GERP RS

5.8

Varity_R

0.53

gMVP

0.58

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