Variant 11-26332014-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001313726.2(ANO3):c.229+22295T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,027,362 control chromosomes in the GnomAD database, including 508,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.98 ( 73118 hom., cov: 34)

Exomes 𝑓: 1.0 ( 435625 hom. )

Consequence

ANO3
NM_001313726.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.382

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:

LOC105376598 (HGNC:):

LOC105376598 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 11-26332014-T-C is Benign according to our data. Variant chr11-26332014-T-C is described in ClinVar as [Benign]. Clinvar id is 1288620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO3	NM_001313726.2 linkuse as main transcript	c.229+22295T>C		intron_variant			NP_001300655.1
LOC105376598	XR_931138.3 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO3	ENST00000525139.5 linkuse as main transcript	c.-3+22295T>C		intron_variant		5		ENSP00000432576
ANO3	ENST00000672621.1 linkuse as main transcript	c.229+22295T>C		intron_variant				ENSP00000500506

Frequencies

GnomAD3 genomes

AF:

0.979

AC:

149052

AN:

152204

Hom.:

73061

Cov.:

show subpopulations

Gnomad AFR

AF:

0.929

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.991

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.985

GnomAD4 exome

AF:

0.998

AC:

873078

AN:

875040

Hom.:

435625

Cov.:

AF XY:

0.998

AC XY:

435679

AN XY:

436556

show subpopulations

Gnomad4 AFR exome

AF:

0.930

Gnomad4 AMR exome

AF:

0.995

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.995

GnomAD4 genome

AF:

0.979

AC:

149168

AN:

152322

Hom.:

73118

Cov.:

AF XY:

0.980

AC XY:

72983

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.929

Gnomad4 AMR

AF:

0.991

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.985

Alfa

AF:

0.997

Hom.:

3321

Bravo

AF:

0.978

Asia WGS

AF:

0.996

AC:

3464

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.92

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