NM_031418.4:c.1290-5_1290-4delTC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_031418.4(ANO3):c.1290-5_1290-4delTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 1,548,830 control chromosomes in the GnomAD database, including 2,171 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 106 hom., cov: 26)

Exomes 𝑓: 0.037 ( 2065 hom. )

Consequence

ANO3
NM_031418.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.576

Publications

1 publications found

Variant links:

Genes affected

ANO3 (HGNC:14004): (anoctamin 3) The protein encoded by this gene belongs to the TMEM16 family of predicted membrane proteins, that are also known as anoctamins. While little is known about the function of this gene, mutations in this gene have been associated with some cases of autosomal dominant craniocervical dystonia. Cells from individuals with a mutation in this gene exhibited abnormalities in endoplasmic reticulum-dependent calcium signaling. Studies in rat show that the rat ortholog of this protein interacts with, and modulates the activity of a sodium-activated potassium channel. Deletion of this gene caused increased pain sensitivity in the rat model system. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

ANO3 Gene-Disease associations (from GenCC):

dystonia 24
Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ANO3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 11-26553241-TTC-T is Benign according to our data. Variant chr11-26553241-TTC-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 412867.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 = 0.027 (4091/151510) while in subpopulation NFE AF = 0.0442 (2993/67768). AF 95% confidence interval is 0.0428. There are 106 homozygotes in GnomAd4. There are 1850 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.

BS2

High AC in GnomAd4 at 4091 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO3	NM_031418.4 link	c.1290-5_1290-4delTC		splice_region_variant, intron_variant	Intron 12 of 26	ENST00000256737.8	NP_113606.2	Q9BYT9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO3	ENST00000256737.8 link	c.1290-7_1290-6delTC		splice_region_variant, intron_variant	Intron 12 of 26	1	NM_031418.4	ENSP00000256737.3		Q9BYT9-1

Frequencies

GnomAD3 genomes

AF:

0.0270

AC:

4089

AN:

151394

Hom.:

106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00734

Gnomad AMI

AF:

0.0243

Gnomad AMR

AF:

0.0172

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0121

Gnomad FIN

AF:

0.0337

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0442

Gnomad OTH

AF:

0.0243

GnomAD2 exomes

AF:

0.0302

AC:

7210

AN:

238746

AF XY:

0.0304

show subpopulations

Gnomad AFR exome

AF:

0.00648

Gnomad AMR exome

AF:

0.0121

Gnomad ASJ exome

AF:

0.0140

Gnomad EAS exome

AF:

0.00103

Gnomad FIN exome

AF:

0.0408

Gnomad NFE exome

AF:

0.0476

Gnomad OTH exome

AF:

0.0277

GnomAD4 exome

AF:

0.0375

AC:

52339

AN:

1397320

Hom.:

2065

AF XY:

0.0365

AC XY:

25484

AN XY:

697920

show subpopulations

African (AFR)

AF:

0.00511

AC:

163

AN:

31906

American (AMR)

AF:

0.0126

AC:

542

AN:

43142

Ashkenazi Jewish (ASJ)

AF:

0.0140

AC:

355

AN:

25330

East Asian (EAS)

AF:

0.000557

AC:

AN:

39522

South Asian (SAS)

AF:

0.0132

AC:

1096

AN:

82946

European-Finnish (FIN)

AF:

0.0443

AC:

2217

AN:

49996

Middle Eastern (MID)

AF:

0.00681

AC:

AN:

5580

European-Non Finnish (NFE)

AF:

0.0436

AC:

46200

AN:

1060770

Other (OTH)

AF:

0.0293

AC:

1706

AN:

58128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

1976

3952

5929

7905

9881

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1572

3144

4716

6288

7860

<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:

0.0270

AC:

4091

AN:

151510

Hom.:

106

Cov.:

AF XY:

0.0250

AC XY:

1850

AN XY:

74022

show subpopulations

African (AFR)

AF:

0.00732

AC:

303

AN:

41382

American (AMR)

AF:

0.0172

AC:

262

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

3468

East Asian (EAS)

AF:

0.00117

AC:

AN:

5140

South Asian (SAS)

AF:

0.0125

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.0337

AC:

352

AN:

10460

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0442

AC:

2993

AN:

67768

Other (OTH)

AF:

0.0241

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

Heterozygous variant carriers

180

360

541

721

901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0318

Hom.:

Bravo

AF:

0.0249

Asia WGS

AF:

0.00867

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

ANO3-related disorder

Benign:1

Mar 27, 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). -

Dystonia 24

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Aug 03, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dystonic disorder

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.58

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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