Variant 3-111981963-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018394.4(ABHD10):c.322A>G(p.Ile108Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 1,546,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ABHD10
NM_018394.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

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:

ABHD10 (HGNC:):

ABHD10 links:

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ACMG classification

Classification made for transcript

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=0.10896051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD10	NM_018394.4 linkuse as main transcript	c.322A>G	p.Ile108Val	missense_variant	2/5	ENST00000273359.8	NP_060864.1	Q9NUJ1-1
ABHD10	NM_001272069.2 linkuse as main transcript	c.322A>G	p.Ile108Val	missense_variant	2/6		NP_001258998.1	Q9NUJ1-3
ABHD10	NR_073570.2 linkuse as main transcript	n.178+2760A>G		intron_variant
ABHD10	NR_073571.2 linkuse as main transcript	n.178+2760A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD10	ENST00000273359.8 linkuse as main transcript	c.322A>G	p.Ile108Val	missense_variant	2/5	1	NM_018394.4	ENSP00000273359.3		Q9NUJ1-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000365

AC:

AN:

246744

Hom.:

AF XY:

0.0000225

AC XY:

AN XY:

133272

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.0000302

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000340

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1393898

Hom.:

Cov.:

AF XY:

0.0000117

AC XY:

AN XY:

685592

show subpopulations

Gnomad4 AFR exome

AF:

0.0000919

Gnomad4 AMR exome

AF:

0.0000230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000397

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000141

Gnomad4 OTH exome

AF:

0.0000351

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

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:

0.0000283

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000247

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

Oct 05, 2021

The c.322A>G (p.I108V) alteration is located in exon 2 (coding exon 2) of the ABHD10 gene. This alteration results from a A to G substitution at nucleotide position 322, causing the isoleucine (I) at amino acid position 108 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

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0076

T;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.066

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.85

D;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.73

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.36

N;N

REVEL

Benign

0.057

Sift

Benign

0.43

T;T

Sift4G

Benign

0.46

T;T

Polyphen

0.15

B;.

Vest4

0.14

MutPred

0.46

Loss of glycosylation at S113 (P = 0.0339);Loss of glycosylation at S113 (P = 0.0339);

MVP

0.51

MPC

0.13

ClinPred

0.055

GERP RS

4.2

Varity_R

0.027

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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