3-43561311-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018075.5(ANO10):c.1385G>A(p.Arg462Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 1,613,842 control chromosomes in the GnomAD database, including 319,572 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27946 hom., cov: 32)

Exomes 𝑓: 0.63 ( 291626 hom. )

Consequence

ANO10
NM_018075.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.106

Publications

38 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive spinocerebellar ataxia 10
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ANO10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.683522E-7).

BP6

Variant 3-43561311-C-T is Benign according to our data. Variant chr3-43561311-C-T is described in ClinVar as Benign. ClinVar VariationId is 128387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO10	NM_018075.5 link	c.1385G>A	p.Arg462Gln	missense_variant	Exon 9 of 13	ENST00000292246.8	NP_060545.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO10	ENST00000292246.8 link	c.1385G>A	p.Arg462Gln	missense_variant	Exon 9 of 13	1	NM_018075.5	ENSP00000292246.3

Frequencies

GnomAD3 genomes

AF:

0.598

AC:

90911

AN:

151942

Hom.:

27926

Cov.:

show subpopulations

Gnomad AFR

AF:

0.500

Gnomad AMI

AF:

0.589

Gnomad AMR

AF:

0.684

Gnomad ASJ

AF:

0.525

Gnomad EAS

AF:

0.890

Gnomad SAS

AF:

0.727

Gnomad FIN

AF:

0.642

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.605

Gnomad OTH

AF:

0.600

GnomAD2 exomes

AF:

0.658

AC:

165338

AN:

251442

AF XY:

0.655

show subpopulations

Gnomad AFR exome

AF:

0.496

Gnomad AMR exome

AF:

0.794

Gnomad ASJ exome

AF:

0.507

Gnomad EAS exome

AF:

0.884

Gnomad FIN exome

AF:

0.635

Gnomad NFE exome

AF:

0.606

Gnomad OTH exome

AF:

0.611

GnomAD4 exome

AF:

0.628

AC:

918204

AN:

1461782

Hom.:

291626

Cov.:

AF XY:

0.629

AC XY:

457574

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.495

AC:

16560

AN:

33478

American (AMR)

AF:

0.778

AC:

34796

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.516

AC:

13479

AN:

26134

East Asian (EAS)

AF:

0.897

AC:

35583

AN:

39684

South Asian (SAS)

AF:

0.714

AC:

61580

AN:

86258

European-Finnish (FIN)

AF:

0.638

AC:

34079

AN:

53418

Middle Eastern (MID)

AF:

0.536

AC:

3089

AN:

5768

European-Non Finnish (NFE)

AF:

0.613

AC:

681652

AN:

1111928

Other (OTH)

AF:

0.619

AC:

37386

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

19789

39578

59368

79157

98946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18536

37072

55608

74144

92680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.598

AC:

90984

AN:

152060

Hom.:

27946

Cov.:

AF XY:

0.606

AC XY:

45085

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.500

AC:

20706

AN:

41446

American (AMR)

AF:

0.684

AC:

10449

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

1821

AN:

3470

East Asian (EAS)

AF:

0.890

AC:

4611

AN:

5180

South Asian (SAS)

AF:

0.727

AC:

3512

AN:

4828

European-Finnish (FIN)

AF:

0.642

AC:

6779

AN:

10560

Middle Eastern (MID)

AF:

0.575

AC:

169

AN:

294

European-Non Finnish (NFE)

AF:

0.605

AC:

41134

AN:

67994

Other (OTH)

AF:

0.600

AC:

1269

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1834

3668

5502

7336

9170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

776

1552

2328

3104

3880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.600

Hom.:

94930

Bravo

AF:

0.595

TwinsUK

AF:

0.609

AC:

2258

ALSPAC

AF:

0.611

AC:

2356

ESP6500AA

AF:

0.498

AC:

2193

ESP6500EA

AF:

0.587

AC:

5050

ExAC

AF:

0.650

AC:

78972

Asia WGS

AF:

0.783

AC:

2722

AN:

3478

EpiCase

AF:

0.596

EpiControl

AF:

0.593

ClinVar

Significance: Benign

Submissions summary: Benign:11

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

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

- -

Jan 12, 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:4

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

- -

Jul 18, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:3

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

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.0

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.051

T;.;.;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.84

T;T;T;T;T

MetaRNN

Benign

6.7e-7

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;.;.;L;.

PhyloP100

-0.11

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.1

N;N;N;N;N

REVEL

Benign

0.089

Sift

Benign

0.24

T;T;T;T;T

Sift4G

Benign

0.32

T;T;T;T;T

Polyphen

0.0010

B;P;B;.;B

Vest4

0.015

MPC

0.11

ClinPred

0.0036

GERP RS

-5.4

Varity_R

0.088

gMVP

0.081

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over