Genetic Variant ABHD5:p.Gln130Arg (chr3-43702470-A-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM5

The ENST00000644371.2(ABHD5):c.389A>G(p.Gln130Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,244 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q130P) has been classified as Pathogenic.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ABHD5
ENST00000644371.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.01

Publications

13 publications found

Variant links:

Genes affected

ABHD5 (HGNC:21396): (abhydrolase domain containing 5, lysophosphatidic acid acyltransferase) The protein encoded by this gene belongs to a large family of proteins defined by an alpha/beta hydrolase fold, and contains three sequence motifs that correspond to a catalytic triad found in the esterase/lipase/thioesterase subfamily. It differs from other members of this subfamily in that its putative catalytic triad contains an asparagine instead of the serine residue. Mutations in this gene have been associated with Chanarin-Dorfman syndrome, a triglyceride storage disease with impaired long-chain fatty acid oxidation. [provided by RefSeq, Jul 2008]

ABHD5 Gene-Disease associations (from GenCC):

Dorfman-Chanarin disease
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

ABHD5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr3-43702470-A-C is described in ClinVar as Pathogenic. ClinVar VariationId is 5350.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000644371.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABHD5	NM_016006.6	MANE Select	c.389A>G	p.Gln130Arg	missense	Exon 3 of 7	NP_057090.2
ABHD5	NM_001355186.2		c.389A>G	p.Gln130Arg	missense	Exon 3 of 8	NP_001342115.1
ABHD5	NM_001365649.1		c.266A>G	p.Gln89Arg	missense	Exon 3 of 7	NP_001352578.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABHD5	ENST00000644371.2	MANE Select	c.389A>G	p.Gln130Arg	missense	Exon 3 of 7	ENSP00000495778.1
ABHD5	ENST00000458276.7	TSL:1	c.389A>G	p.Gln130Arg	missense	Exon 3 of 6	ENSP00000390849.3
ABHD5	ENST00000454293.2	TSL:3	c.266A>G	p.Gln89Arg	missense	Exon 3 of 8	ENSP00000412014.2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.7

PhyloP100

7.0

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.34

Sift

Benign

0.043

Sift4G

Benign

0.28

Polyphen

0.57

Vest4

0.77

MutPred

0.60

Loss of disorder (P = 0.2207)

MVP

0.69

MPC

0.30

ClinPred

0.95

GERP RS

5.8

Varity_R

0.78

gMVP

0.96

Mutation Taster

=30/70

disease causing

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over