Genetic Variant ABHD6:p.Arg244Gln (chr3-58285134-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001320126.2(ABHD6):c.731G>A(p.Arg244Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ABHD6
NM_001320126.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15

Publications

1 publications found

Variant links:

Genes affected

ABHD6 (HGNC:21398): (abhydrolase domain containing 6, acylglycerol lipase) Enables acylglycerol lipase activity. Involved in acylglycerol catabolic process. Predicted to be located in late endosome membrane and lysosomal membrane. Predicted to be integral component of membrane. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in GABA-ergic synapse; glutamatergic synapse; and mitochondrion. Predicted to be integral component of postsynaptic membrane. [provided by Alliance of Genome Resources, Apr 2022]

ABHD6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.747

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320126.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD6	NM_001320126.2	MANE Select	c.731G>A	p.Arg244Gln	missense	Exon 8 of 10	NP_001307055.1	Q9BV23
	ABHD6	NM_020676.7		c.731G>A	p.Arg244Gln	missense	Exon 7 of 9	NP_065727.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABHD6	ENST00000478253.6	TSL:2 MANE Select	c.731G>A	p.Arg244Gln	missense	Exon 8 of 10	ENSP00000420315.1	Q9BV23
ABHD6	ENST00000295962.8	TSL:1	c.731G>A	p.Arg244Gln	missense	Exon 7 of 9	ENSP00000295962.4	Q9BV23
ABHD6	ENST00000972009.1		c.845G>A	p.Arg282Gln	missense	Exon 8 of 10	ENSP00000642068.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251490

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000752

AC:

AN:

1461794

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111928

Other (OTH)

AF:

0.0000166

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.0019

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.089

Eigen

Benign

-0.046

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.011

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

PhyloP100

6.2

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.61

REVEL

Benign

0.17

Sift

Benign

0.32

Sift4G

Benign

0.63

Polyphen

0.068

Vest4

0.73

MutPred

0.68

Loss of methylation at R244 (P = 0.0344)

MVP

0.82

MPC

0.25

ClinPred

0.61

GERP RS

5.7

Varity_R

0.11

gMVP

0.58

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over