3-43372790-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018075.5(ANO10):c.1915-5816C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,511,604 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 4 hom. )

Consequence

ANO10
NM_018075.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.363

Publications

2 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 links:

SNRK (HGNC:30598): (SNF related kinase) SNRK is a member of the sucrose nonfermenting (SNF)-related kinase family of serine/threonine kinases (Kertesz et al., 2002 [PubMed 12234663]).[supplied by OMIM, Apr 2009]

SNRK 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=0.0049410462).

BP6

Variant 3-43372790-G-T is Benign according to our data. Variant chr3-43372790-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 425294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00204 (311/152330) while in subpopulation NFE AF = 0.00245 (167/68036). AF 95% confidence interval is 0.00215. There are 1 homozygotes in GnomAd4. There are 171 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO10	NM_018075.5 link	c.1915-5816C>A		intron_variant	Intron 12 of 12	ENST00000292246.8	NP_060545.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO10	ENST00000292246.8 link	c.1915-5816C>A		intron_variant	Intron 12 of 12	1	NM_018075.5	ENSP00000292246.3

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

311

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00867

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00245

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00167

AC:

214

AN:

128382

AF XY:

0.00174

show subpopulations

Gnomad AFR exome

AF:

0.000328

Gnomad AMR exome

AF:

0.000698

Gnomad ASJ exome

AF:

0.00235

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00928

Gnomad NFE exome

AF:

0.00239

Gnomad OTH exome

AF:

0.00300

GnomAD4 exome

AF:

0.00214

AC:

2914

AN:

1359274

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

1419

AN XY:

672112

show subpopulations

African (AFR)

AF:

0.000354

AC:

AN:

31114

American (AMR)

AF:

0.000561

AC:

AN:

35678

Ashkenazi Jewish (ASJ)

AF:

0.00272

AC:

AN:

25010

East Asian (EAS)

AF:

0.00

AC:

AN:

35614

South Asian (SAS)

AF:

0.00

AC:

AN:

78752

European-Finnish (FIN)

AF:

0.00732

AC:

245

AN:

33458

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

0.00235

AC:

2479

AN:

1056856

Other (OTH)

AF:

0.00159

AC:

AN:

57154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

130

261

391

522

652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

264

352

440

<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:

0.00204

AC:

311

AN:

152330

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

171

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41566

American (AMR)

AF:

0.000980

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00867

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00245

AC:

167

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00132

Hom.:

Bravo

AF:

0.00121

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00285

AC:

ExAC

AF:

0.000251

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 24, 2024

Athena Diagnostics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ANO10-related disorder

Benign:1

Oct 08, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

not provided

Benign:1

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ANO10: BP4, BS2

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.35

(source)

DANN

Benign

0.85

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.23

M_CAP

Benign

0.0043

MetaRNN

Benign

0.0049

MetaSVM

Benign

-1.0

PhyloP100

-0.36

PROVEAN

Benign

-1.2

REVEL

Benign

0.098

Sift

Pathogenic

0.0

Vest4

0.092

ClinPred

0.026

GERP RS

-1.5

Mutation Taster

=98/2

polymorphism

(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

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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