Genetic Variant NM_016006.6:c.14A>G (chr3-43691006-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_016006.6(ABHD5):c.14A>G(p.Glu5Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. E5A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ABHD5
NM_016006.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.353

Publications

2 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 links:

ANO10 (HGNC:25519): (anoctamin 10) The transmembrane protein encoded by this gene belongs to the anoctamin family of calcium-activated chloride channels, also known as the transmembrane 16 family. The encoded protein contains eight transmembrane domains with cytosolic N- and C-termini. Defects in this gene may cause autosomal recessive spinocerebellar ataxia-10. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ANO10 Gene-Disease associations (from GenCC):

autosomal recessive spinocerebellar ataxia 10
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ANO10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27279156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABHD5	NM_016006.6 link	c.14A>G	p.Glu5Gly	missense_variant	Exon 1 of 7	ENST00000644371.2	NP_057090.2	Q8WTS1A0A0S2Z5D6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABHD5	ENST00000644371.2 link	c.14A>G	p.Glu5Gly	missense_variant	Exon 1 of 7		NM_016006.6	ENSP00000495778.1		Q8WTS1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1416796

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704918

African (AFR)

AF:

0.00

AC:

AN:

29340

American (AMR)

AF:

0.00

AC:

AN:

39874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24772

East Asian (EAS)

AF:

0.00

AC:

AN:

34430

South Asian (SAS)

AF:

0.00

AC:

AN:

81994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49926

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092476

Other (OTH)

AF:

0.00

AC:

AN:

58374

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Uncertain

0.098

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.61

.;T

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.0

N;.

PhyloP100

0.35

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.82

.;N

REVEL

Uncertain

0.47

Sift

Benign

0.039

.;D

Sift4G

Benign

0.14

.;T

Polyphen

0.59

P;.

Vest4

0.37

MutPred

0.20

Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);

MVP

0.84

MPC

0.17

ClinPred

0.22

GERP RS

3.0

PromoterAI

0.091

Neutral

(source)

Varity_R

0.14

gMVP

0.56

Mutation Taster

=80/20

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over