Variant 3-43691011-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_016006.6(ABHD5):c.19G>A(p.Glu7Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 1,569,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

ABHD5
NM_016006.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter P:1B:1

Conservation

PhyloP100: -0.101

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042927384).

BP6

Variant 3-43691011-G-A is Benign according to our data. Variant chr3-43691011-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 5351.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD5	NM_016006.6 linkuse as main transcript	c.19G>A	p.Glu7Lys	missense_variant	1/7	ENST00000644371.2	NP_057090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD5	ENST00000644371.2 linkuse as main transcript	c.19G>A	p.Glu7Lys	missense_variant	1/7		NM_016006.6	ENSP00000495778	P1

Frequencies

GnomAD3 genomes

AF:

0.000796

AC:

121

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00283

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:

0.0000294

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.000135

AC:

AN:

200580

Hom.:

AF XY:

0.000107

AC XY:

AN XY:

111798

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.000103

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.0000804

AC:

114

AN:

1417116

Hom.:

Cov.:

AF XY:

0.0000837

AC XY:

AN XY:

705094

show subpopulations

Gnomad4 AFR exome

AF:

0.00321

Gnomad4 AMR exome

AF:

0.000151

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000458

Gnomad4 OTH exome

AF:

0.000137

GnomAD4 genome

AF:

0.000796

AC:

121

AN:

152058

Hom.:

Cov.:

AF XY:

0.000632

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00282

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:

0.0000294

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.000269

Hom.:

Bravo

AF:

0.000805

ESP6500AA

AF:

0.00160

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000166

AC:

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Triglyceride storage disease with ichthyosis

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2001

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 25, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.75

.;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

4.7e-8

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.48

.;N

REVEL

Benign

0.25

Sift

Benign

0.36

.;T

Sift4G

Benign

0.85

.;T

Polyphen

0.044

B;.

Vest4

0.28

MVP

0.39

MPC

0.17

ClinPred

0.022

GERP RS

-0.13

Varity_R

0.16

gMVP

0.56

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

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