Variant 3-111986312-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000273359.8(ABHD10):c.375C>A(p.Ser125Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,716 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: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ABHD10
ENST00000273359.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.238

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 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=0.12153649).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ABHD10	NM_018394.4 linkuse as main transcript	c.375C>A	p.Ser125Arg	missense_variant	3/5	ENST00000273359.8	NP_060864.1
ABHD10	NM_001272069.2 linkuse as main transcript	c.375C>A	p.Ser125Arg	missense_variant	3/6		NP_001258998.1
ABHD10	NR_073570.2 linkuse as main transcript	n.227C>A		non_coding_transcript_exon_variant	2/4
ABHD10	NR_073571.2 linkuse as main transcript	n.179-602C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD10	ENST00000273359.8 linkuse as main transcript	c.375C>A	p.Ser125Arg	missense_variant	3/5	1	NM_018394.4	ENSP00000273359	P1	Q9NUJ1-1
ABHD10	ENST00000494817.1 linkuse as main transcript	c.375C>A	p.Ser125Arg	missense_variant	3/6	3		ENSP00000418973		Q9NUJ1-3
ABHD10	ENST00000491580.1 linkuse as main transcript	c.191C>A	p.Ala64Glu	missense_variant, NMD_transcript_variant	2/4	2		ENSP00000418162
ABHD10	ENST00000493784.1 linkuse as main transcript	c.143-602C>A		intron_variant, NMD_transcript_variant		3		ENSP00000417880

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251414

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

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:

0.00000410

AC:

AN:

1461716

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

May 26, 2024

The c.375C>A (p.S125R) alteration is located in exon 3 (coding exon 3) of the ABHD10 gene. This alteration results from a C to A substitution at nucleotide position 375, causing the serine (S) at amino acid position 125 to be replaced by an arginine (R). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.017

T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.036

Sift

Benign

0.29

T;T

Sift4G

Benign

0.42

T;T

Polyphen

0.47

P;.

Vest4

0.36

MutPred

0.39

Gain of glycosylation at S122 (P = 0.0199);Gain of glycosylation at S122 (P = 0.0199);

MVP

0.73

MPC

0.19

ClinPred

0.12

GERP RS

2.6

Varity_R

0.091

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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