Variant 11-26332404-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_031418.4(ANO3):c.46+83G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,360,684 control chromosomes in the GnomAD database, including 64,044 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6019 hom., cov: 26)

Exomes 𝑓: 0.31 ( 58025 hom. )

Consequence

ANO3
NM_031418.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.00

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 11-26332404-G-T is Benign according to our data. Variant chr11-26332404-G-T is described in ClinVar as [Benign]. Clinvar id is 1249245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ANO3	NM_031418.4 linkuse as main transcript	c.46+83G>T	intron_variant	ENST00000256737.8
ANO3	NM_001313726.2 linkuse as main transcript	c.229+22685G>T	intron_variant
ANO3	XM_047427399.1 linkuse as main transcript	c.46+83G>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ANO3	ENST00000256737.8 linkuse as main transcript	c.46+83G>T	intron_variant	1	NM_031418.4	P3	Q9BYT9-1
ANO3	ENST00000525139.5 linkuse as main transcript	c.-3+22685G>T	intron_variant	5
ANO3	ENST00000531646.1 linkuse as main transcript	c.46+83G>T	intron_variant	4
ANO3	ENST00000672621.1 linkuse as main transcript	c.229+22685G>T	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

41641

AN:

148684

Hom.:

6017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.187

Gnomad AMR

AF:

0.244

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.327

Gnomad FIN

AF:

0.367

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.265

GnomAD4 exome

AF:

0.307

AC:

371609

AN:

1211884

Hom.:

58025

AF XY:

0.308

AC XY:

189796

AN XY:

615272

show subpopulations

Gnomad4 AFR exome

AF:

0.227

Gnomad4 AMR exome

AF:

0.263

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.344

Gnomad4 FIN exome

AF:

0.381

Gnomad4 NFE exome

AF:

0.312

Gnomad4 OTH exome

AF:

0.296

GnomAD4 genome

AF:

0.280

AC:

41673

AN:

148800

Hom.:

6019

Cov.:

AF XY:

0.281

AC XY:

20335

AN XY:

72250

show subpopulations

Gnomad4 AFR

AF:

0.230

Gnomad4 AMR

AF:

0.244

Gnomad4 ASJ

AF:

0.236

Gnomad4 EAS

AF:

0.169

Gnomad4 SAS

AF:

0.328

Gnomad4 FIN

AF:

0.367

Gnomad4 NFE

AF:

0.314

Gnomad4 OTH

AF:

0.265

Alfa

AF:

0.304

Hom.:

12341

Bravo

AF:

0.272

Asia WGS

AF:

0.268

AC:

930

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Dystonia 24

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.0

DANN

Benign

0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over