3-43690974-C-T

Position:

chr3-43690974-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016006.6(ABHD5):c.-19C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 1,568,598 control chromosomes in the GnomAD database, including 894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 56 hom., cov: 32)

Exomes 𝑓: 0.028 ( 838 hom. )

Consequence

ABHD5
NM_016006.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.30

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 3-43690974-C-T is Benign according to our data. Variant chr3-43690974-C-T is described in ClinVar as [Benign]. Clinvar id is 345213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0846 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.-19C>T		5_prime_UTR_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.-19C>T		5_prime_UTR_variant	1/7		NM_016006.6	P1

Frequencies

GnomAD3 genomes

AF:

0.0211

AC:

3209

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00785

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0233

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.0268

Gnomad SAS

AF:

0.0916

Gnomad FIN

AF:

0.00500

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.0256

Gnomad OTH

AF:

0.0249

GnomAD3 exomes

AF:

0.0320

AC:

6336

AN:

197706

Hom.:

183

AF XY:

0.0363

AC XY:

4005

AN XY:

110294

show subpopulations

Gnomad AFR exome

AF:

0.00818

Gnomad AMR exome

AF:

0.0285

Gnomad ASJ exome

AF:

0.0300

Gnomad EAS exome

AF:

0.0216

Gnomad SAS exome

AF:

0.0943

Gnomad FIN exome

AF:

0.00739

Gnomad NFE exome

AF:

0.0241

Gnomad OTH exome

AF:

0.0267

GnomAD4 exome

AF:

0.0281

AC:

39762

AN:

1416490

Hom.:

838

Cov.:

AF XY:

0.0302

AC XY:

21256

AN XY:

704468

show subpopulations

Gnomad4 AFR exome

AF:

0.00667

Gnomad4 AMR exome

AF:

0.0301

Gnomad4 ASJ exome

AF:

0.0312

Gnomad4 EAS exome

AF:

0.0300

Gnomad4 SAS exome

AF:

0.0904

Gnomad4 FIN exome

AF:

0.00746

Gnomad4 NFE exome

AF:

0.0245

Gnomad4 OTH exome

AF:

0.0307

GnomAD4 genome

AF:

0.0211

AC:

3214

AN:

152108

Hom.:

Cov.:

AF XY:

0.0214

AC XY:

1593

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00799

Gnomad4 AMR

AF:

0.0233

Gnomad4 ASJ

AF:

0.0268

Gnomad4 EAS

AF:

0.0265

Gnomad4 SAS

AF:

0.0917

Gnomad4 FIN

AF:

0.00500

Gnomad4 NFE

AF:

0.0256

Gnomad4 OTH

AF:

0.0247

Alfa

AF:

0.0222

Hom.:

Bravo

AF:

0.0202

Asia WGS

AF:

0.0460

AC:

158

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.74

CADD

Benign

0.28

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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