rs117748217

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_031418.4(ANO3):c.2811C>T(p.Asp937Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00945 in 1,613,220 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0096 ( 111 hom. )

Consequence

ANO3
NM_031418.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.861

Publications

4 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 11-26660309-C-T is Benign according to our data. Variant chr11-26660309-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 412868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.861 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00754 (1148/152220) while in subpopulation AMR AF = 0.014 (214/15260). AF 95% confidence interval is 0.0125. There are 11 homozygotes in GnomAd4. There are 525 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1148 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO3	NM_031418.4 link	c.2811C>T	p.Asp937Asp	synonymous_variant	Exon 27 of 27	ENST00000256737.8	NP_113606.2	Q9BYT9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ANO3	ENST00000256737.8 link	c.2811C>T	p.Asp937Asp	synonymous_variant	Exon 27 of 27	1	NM_031418.4	ENSP00000256737.3	Q9BYT9-1
ANO3	ENST00000672621.1 link	c.2994C>T	p.Asp998Asp	synonymous_variant	Exon 28 of 28			ENSP00000500506.1	A0A5F9ZHL6
ANO3	ENST00000525139.5 link	c.2763C>T	p.Asp921Asp	synonymous_variant	Exon 27 of 27	5		ENSP00000432576.1	E9PQ79
ANO3	ENST00000531568.1 link	c.2373C>T	p.Asp791Asp	synonymous_variant	Exon 24 of 24	2		ENSP00000432394.1	Q9BYT9-2

Frequencies

GnomAD3 genomes

AF:

0.00754

AC:

1147

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0140

Gnomad ASJ

AF:

0.0380

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00745

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00906

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00873

AC:

2189

AN:

250776

AF XY:

0.00913

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.0324

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.000785

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.0142

GnomAD4 exome

AF:

0.00965

AC:

14097

AN:

1461000

Hom.:

111

Cov.:

AF XY:

0.00966

AC XY:

7020

AN XY:

726792

show subpopulations

African (AFR)

AF:

0.00236

AC:

AN:

33420

American (AMR)

AF:

0.0118

AC:

529

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.0340

AC:

887

AN:

26110

East Asian (EAS)

AF:

0.000126

AC:

AN:

39676

South Asian (SAS)

AF:

0.00634

AC:

546

AN:

86074

European-Finnish (FIN)

AF:

0.00137

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.0375

AC:

216

AN:

5758

European-Non Finnish (NFE)

AF:

0.00993

AC:

11040

AN:

1111534

Other (OTH)

AF:

0.0120

AC:

722

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

699

1399

2098

2798

3497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.00754

AC:

1148

AN:

152220

Hom.:

Cov.:

AF XY:

0.00705

AC XY:

525

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.00221

AC:

AN:

41548

American (AMR)

AF:

0.0140

AC:

214

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.0380

AC:

132

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.00725

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00907

AC:

617

AN:

68010

Other (OTH)

AF:

0.0104

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

127

190

254

317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0101

Hom.:

Bravo

AF:

0.00879

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0123

EpiControl

AF:

0.0144

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 09, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ANO3: BP4, BP7, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dystonia 24

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: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

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.61

PhyloP100

0.86

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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