Genetic Variant ANO3:c.1448-14581T>C (chr11-26583784-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_031418.4(ANO3):c.1448-14581T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,158 control chromosomes in the GnomAD database, including 1,038 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1038 hom., cov: 32)

Consequence

ANO3
NM_031418.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0310

Publications

11 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:

LOC124902648 (HGNC:):

LOC124902648 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO3	NM_031418.4 link	c.1448-14581T>C		intron_variant	Intron 14 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.1448-14581T>C	intron_variant	Intron 14 of 26	1	NM_031418.4	ENSP00000256737.3	Q9BYT9-1
ANO3	ENST00000672621.1 link	c.1631-14581T>C	intron_variant	Intron 15 of 27			ENSP00000500506.1	A0A5F9ZHL6
ANO3	ENST00000525139.5 link	c.1400-14581T>C	intron_variant	Intron 14 of 26	5		ENSP00000432576.1	E9PQ79
ANO3	ENST00000531568.1 link	c.1010-14581T>C	intron_variant	Intron 11 of 23	2		ENSP00000432394.1	Q9BYT9-2

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16180

AN:

152040

Hom.:

1037

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0939

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.0801

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.0804

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0970

Gnomad OTH

AF:

0.106

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.106

AC:

16195

AN:

152158

Hom.:

1038

Cov.:

AF XY:

0.108

AC XY:

8067

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0941

AC:

3909

AN:

41524

American (AMR)

AF:

0.104

AC:

1595

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0801

AC:

278

AN:

3470

East Asian (EAS)

AF:

0.341

AC:

1748

AN:

5132

South Asian (SAS)

AF:

0.0801

AC:

386

AN:

4820

European-Finnish (FIN)

AF:

0.123

AC:

1302

AN:

10610

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0970

AC:

6594

AN:

67996

Other (OTH)

AF:

0.105

AC:

221

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

724

1448

2172

2896

3620

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

178

356

534

712

890

<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:

0.104

Hom.:

4035

Bravo

AF:

0.109

Asia WGS

AF:

0.193

AC:

669

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.7

(source)

DANN

Benign

0.73

PhyloP100

-0.031

Mutation Taster

=100/0

polymorphism (auto)

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over