3-43691004-G-A

Position:

chr3-43691004-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016006.6(ABHD5):c.12G>A(p.Glu4=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0276 in 1,569,968 control chromosomes in the GnomAD database, including 897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 60 hom., cov: 32)

Exomes 𝑓: 0.028 ( 837 hom. )

Consequence

ABHD5
NM_016006.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.73

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 3-43691004-G-A is Benign according to our data. Variant chr3-43691004-G-A is described in ClinVar as [Benign]. Clinvar id is 345214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-43691004-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.73 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABHD5	NM_016006.6 linkuse as main transcript	c.12G>A	p.Glu4=	synonymous_variant	1/7	ENST00000644371.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABHD5	ENST00000644371.2 linkuse as main transcript	c.12G>A	p.Glu4=	synonymous_variant	1/7		NM_016006.6	P1

Frequencies

GnomAD3 genomes

AF:

0.0225

AC:

3420

AN:

151932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0233

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.0269

Gnomad SAS

AF:

0.0919

Gnomad FIN

AF:

0.00500

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.0256

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.0324

AC:

6431

AN:

198706

Hom.:

188

AF XY:

0.0366

AC XY:

4054

AN XY:

110884

show subpopulations

Gnomad AFR exome

AF:

0.0130

Gnomad AMR exome

AF:

0.0288

Gnomad ASJ exome

AF:

0.0305

Gnomad EAS exome

AF:

0.0219

Gnomad SAS exome

AF:

0.0951

Gnomad FIN exome

AF:

0.00749

Gnomad NFE exome

AF:

0.0240

Gnomad OTH exome

AF:

0.0275

GnomAD4 exome

AF:

0.0282

AC:

39971

AN:

1417930

Hom.:

837

Cov.:

AF XY:

0.0303

AC XY:

21360

AN XY:

705312

show subpopulations

Gnomad4 AFR exome

AF:

0.0124

Gnomad4 AMR exome

AF:

0.0304

Gnomad4 ASJ exome

AF:

0.0312

Gnomad4 EAS exome

AF:

0.0301

Gnomad4 SAS exome

AF:

0.0903

Gnomad4 FIN exome

AF:

0.00750

Gnomad4 NFE exome

AF:

0.0245

Gnomad4 OTH exome

AF:

0.0313

GnomAD4 genome

AF:

0.0226

AC:

3429

AN:

152038

Hom.:

Cov.:

AF XY:

0.0226

AC XY:

1676

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0131

Gnomad4 AMR

AF:

0.0233

Gnomad4 ASJ

AF:

0.0268

Gnomad4 EAS

AF:

0.0266

Gnomad4 SAS

AF:

0.0918

Gnomad4 FIN

AF:

0.00500

Gnomad4 NFE

AF:

0.0256

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0236

Hom.:

Bravo

AF:

0.0218

Asia WGS

AF:

0.0470

AC:

161

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Triglyceride storage disease with ichthyosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

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