3-43690823-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001346468.2(ANO10):c.-12+694C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 554,752 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (3 hom.)
• Consequence: ANO10 NM_001346468.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.01

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=-0.77).
• BP6: Variant 3-43690823-G-A is Benign according to our data. Variant chr3-43690823-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1218949.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00395 (601/152266) while in subpopulation AFR AF= 0.0138 (573/41568). AF 95% confidence interval is 0.0129. There are 8 homozygotes in gnomad4. There are 310 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO10	NM_001346468.2	c.-12+694C>T		intron_variant
ANO10	NM_001346469.2	c.-12+694C>T		intron_variant
ABHD5	NM_001365650.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO10	ENST00000413397.5	c.-12+694C>T		intron_variant		4
ANO10	ENST00000439141.5	c.-106+694C>T		intron_variant		4
ABHD5	ENST00000456453.5	c.-77+113G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.00392 AC: 597 AN: 152154 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.000507 AC: 204 AN: 402486 Hom.: 3 Cov.: 6 AF XY: 0.000436 AC XY: 90 AN XY: 206546

Gnomad4 AFR exome AF: 0.0147

Gnomad4 AMR exome AF: 0.00234

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000222

Gnomad4 SAS exome AF: 0.0000487

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000598

Gnomad4 OTH exome AF: 0.00157

GnomAD4 genome AF: 0.00395 AC: 601 AN: 152266 Hom.: 8 Cov.: 32 AF XY: 0.00416 AC XY: 310 AN XY: 74450

Gnomad4 AFR AF: 0.0138

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00395 Hom.: 0

Bravo AF: 0.00448

Asia WGS AF: 0.00144 AC: 5 AN: 3478

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

Sep 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	6.6
Dann	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs182329157; hg19: chr3-43732315;