3-43690699-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000456453.5(ABHD5):c.-88T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 388,780 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (60 hom., cov: 32)
  • Exomes 𝑓: 0.023 (96 hom.)
• Consequence: ABHD5 ENST00000456453.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.101

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-43690699-T-A is Benign according to our data. Variant chr3-43690699-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 673914.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO10	NM_001346468.2	c.-12+818A>T		intron_variant
ANO10	NM_001346469.2	c.-12+818A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO10	ENST00000428831.1	c.-190A>T		5_prime_UTR_variant	1/4	5
ANO10	ENST00000436073.1	c.-261A>T		5_prime_UTR_variant	1/3	4
ABHD5	ENST00000456453.5	c.-88T>A		5_prime_UTR_variant	2/4	4

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3425 AN: 152200 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0276

Gnomad SAS AF: 0.0915

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0273

GnomAD4 exome AF: 0.0235 AC: 5556 AN: 236462 Hom.: 96 Cov.: 0 AF XY: 0.0241 AC XY: 2908 AN XY: 120842

Gnomad4 AFR exome AF: 0.0123

Gnomad4 AMR exome AF: 0.0370

Gnomad4 ASJ exome AF: 0.0299

Gnomad4 EAS exome AF: 0.0306

Gnomad4 SAS exome AF: 0.0568

Gnomad4 FIN exome AF: 0.00628

Gnomad4 NFE exome AF: 0.0229

Gnomad4 OTH exome AF: 0.0248

GnomAD4 genome AF: 0.0226 AC: 3435 AN: 152318 Hom.: 60 Cov.: 32 AF XY: 0.0226 AC XY: 1680 AN XY: 74496

Gnomad4 AFR AF: 0.0131

Gnomad4 AMR AF: 0.0234

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.0273

Gnomad4 SAS AF: 0.0915

Gnomad4 FIN AF: 0.00499

Gnomad4 NFE AF: 0.0255

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0218 Hom.: 7

Bravo AF: 0.0218

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.9
Dann	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs79739454; hg19: chr3-43732191;