3-43561311-C-T

Position:

chr3-43561311-C-T

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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

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 (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 id is 128387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-43561311-C-T is described in Lovd as [Benign].

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/exons	MANE	UniProt
ANO10	NM_018075.5 linkuse as main transcript	c.1385G>A	p.Arg462Gln	missense_variant	9/13	ENST00000292246.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO10	ENST00000292246.8 linkuse as main transcript	c.1385G>A	p.Arg462Gln	missense_variant	9/13	1	NM_018075.5	P1	Q9NW15-1

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

GnomAD3 exomes

AF:

0.658

AC:

165338

AN:

251442

Hom.:

55873

AF XY:

0.655

AC XY:

89039

AN XY:

135900

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 SAS exome

AF:

0.721

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

Gnomad4 AFR exome

AF:

0.495

Gnomad4 AMR exome

AF:

0.778

Gnomad4 ASJ exome

AF:

0.516

Gnomad4 EAS exome

AF:

0.897

Gnomad4 SAS exome

AF:

0.714

Gnomad4 FIN exome

AF:

0.638

Gnomad4 NFE exome

AF:

0.613

Gnomad4 OTH exome

AF:

0.619

GnomAD4 genome

AF:

0.598

AC:

90984

AN:

152060

Hom.:

27946

Cov.:

AF XY:

0.606

AC XY:

45085

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.500

Gnomad4 AMR

AF:

0.684

Gnomad4 ASJ

AF:

0.525

Gnomad4 EAS

AF:

0.890

Gnomad4 SAS

AF:

0.727

Gnomad4 FIN

AF:

0.642

Gnomad4 NFE

AF:

0.605

Gnomad4 OTH

AF:

0.600

Alfa

AF:

0.601

Hom.:

61003

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

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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	- -

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 18, 2019	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 25, 2019	- -

not specified

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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

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;.

MutationTaster

Benign

1.0

P;P;P;P;P

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

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