3-43565644-T-C

Position:

• chr3-43565644-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018075.5(ANO10):​c.1293+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 1,563,326 control chromosomes in the GnomAD database, including 305,625 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (26101 hom., cov: 28)
  • Exomes 𝑓: 0.62 (279524 hom.)
• Consequence: ANO10 NM_018075.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.295

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-43565644-T-C is Benign according to our data. Variant chr3-43565644-T-C is described in ClinVar as [Benign]. Clinvar id is 260993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-43565644-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO10	NM_018075.5	c.1293+9A>G		intron_variant		ENST00000292246.8	NP_060545.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO10	ENST00000292246.8	c.1293+9A>G		intron_variant		1	NM_018075.5	ENSP00000292246.3

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86769 AN: 151300 Hom.: 26086 Cov.: 28

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.582

GnomAD3 exomes AF: 0.656 AC: 120329 AN: 183444 Hom.: 40784 AF XY: 0.656 AC XY: 63670 AN XY: 97022

Gnomad AFR exome AF: 0.408

Gnomad AMR exome AF: 0.788

Gnomad ASJ exome AF: 0.506

Gnomad EAS exome AF: 0.885

Gnomad SAS exome AF: 0.726

Gnomad FIN exome AF: 0.635

Gnomad NFE exome AF: 0.603

Gnomad OTH exome AF: 0.601

GnomAD4 exome AF: 0.625 AC: 882391 AN: 1411910 Hom.: 279524 Cov.: 32 AF XY: 0.627 AC XY: 437354 AN XY: 697846

Gnomad4 AFR exome AF: 0.405

Gnomad4 AMR exome AF: 0.769

Gnomad4 ASJ exome AF: 0.516

Gnomad4 EAS exome AF: 0.898

Gnomad4 SAS exome AF: 0.721

Gnomad4 FIN exome AF: 0.637

Gnomad4 NFE exome AF: 0.613

Gnomad4 OTH exome AF: 0.612

GnomAD4 genome AF: 0.573 AC: 86832 AN: 151416 Hom.: 26101 Cov.: 28 AF XY: 0.582 AC XY: 43104 AN XY: 74018

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.732

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.583

Alfa AF: 0.595 Hom.: 53989

Bravo AF: 0.566

Asia WGS AF: 0.781 AC: 2715 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal recessive spinocerebellar ataxia 10 Benign:4

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 25, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 21, 2019	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.1
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs7616708; hg19: chr3-43607136;