Genetic Variant NM_018075.5:c.1293+9A>G (chr3-43565644-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.295

Variant links:

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]

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=-0.85).

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 rank	MANE	Protein	UniProt
ANO10	NM_018075.5 link	c.1293+9A>G		intron_variant	Intron 8 of 12	ENST00000292246.8	NP_060545.3	Q9NW15-1A0A024R2S0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO10	ENST00000292246.8 link	c.1293+9A>G		intron_variant	Intron 8 of 12	1	NM_018075.5	ENSP00000292246.3		Q9NW15-1

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

86769

AN:

151300

Hom.:

26086

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.627

AC XY:

437354

AN XY:

697846

show subpopulations

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.:

AF XY:

0.582

AC XY:

43104

AN XY:

74018

show subpopulations

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

LINK: link

Submissions by phenotype

Autosomal recessive spinocerebellar ataxia 10

Benign:4

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided

Benign:3

Sep 25, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 21, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

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