rs3802751

Variant names:

Variant summary

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

The NM_031418.4(ANO3):c.977-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00571 in 1,610,656 control chromosomes in the GnomAD database, including 311 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 30 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 281 hom. )

Consequence

ANO3
NM_031418.4 splice_region, intron

Scores

Splicing: ADA: 0.00006558

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.106

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 11-26537400-T-C is Benign according to our data. Variant chr11-26537400-T-C is described in ClinVar as Benign. ClinVar VariationId is 412869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.073 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO3	NM_031418.4 link	c.977-6T>C		splice_region_variant, intron_variant	Intron 9 of 26	ENST00000256737.8	NP_113606.2	Q9BYT9-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ANO3	ENST00000256737.8 link	c.977-6T>C	splice_region_variant, intron_variant	Intron 9 of 26	1	NM_031418.4	ENSP00000256737.3	Q9BYT9-1
ANO3	ENST00000672621.1 link	c.1160-6T>C	splice_region_variant, intron_variant	Intron 10 of 27			ENSP00000500506.1	A0A5F9ZHL6
ANO3	ENST00000525139.5 link	c.929-6T>C	splice_region_variant, intron_variant	Intron 9 of 26	5		ENSP00000432576.1	E9PQ79
ANO3	ENST00000531568.1 link	c.539-6T>C	splice_region_variant, intron_variant	Intron 6 of 23	2		ENSP00000432394.1	Q9BYT9-2

Frequencies

GnomAD3 genomes

AF:

0.00785

AC:

1194

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0148

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.0790

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0403

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.0116

AC:

2914

AN:

251374

AF XY:

0.0103

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0155

Gnomad ASJ exome

AF:

0.00466

Gnomad EAS exome

AF:

0.0699

Gnomad FIN exome

AF:

0.0345

Gnomad NFE exome

AF:

0.00147

Gnomad OTH exome

AF:

0.00685

GnomAD4 exome

AF:

0.00549

AC:

8004

AN:

1458342

Hom.:

281

Cov.:

AF XY:

0.00536

AC XY:

3892

AN XY:

725758

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33414

American (AMR)

AF:

0.0154

AC:

689

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00345

AC:

AN:

26114

East Asian (EAS)

AF:

0.104

AC:

4112

AN:

39668

South Asian (SAS)

AF:

0.00303

AC:

261

AN:

86188

European-Finnish (FIN)

AF:

0.0331

AC:

1768

AN:

53404

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000689

AC:

764

AN:

1108812

Other (OTH)

AF:

0.00498

AC:

300

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

402

804

1206

1608

2010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<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:

0.00785

AC:

1196

AN:

152314

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

793

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41568

American (AMR)

AF:

0.0148

AC:

226

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

3468

East Asian (EAS)

AF:

0.0793

AC:

411

AN:

5180

South Asian (SAS)

AF:

0.00372

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0403

AC:

428

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00109

AC:

AN:

68024

Other (OTH)

AF:

0.00709

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

129

194

258

323

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:

0.00248

Hom.:

Bravo

AF:

0.00593

Asia WGS

AF:

0.0360

AC:

124

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.000416

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Sep 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dystonic disorder

Benign:1

Feb 03, 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

-0.72

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000066

dbscSNV1_RF

Benign

0.0

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