Variant 11-26553243-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The ENST00000256737.8(ANO3):c.1290-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0084 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

ANO3
ENST00000256737.8 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003468

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.576

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 11-26553243-C-T is Benign according to our data. Variant chr11-26553243-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 455985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO3	NM_031418.4 linkuse as main transcript	c.1290-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000256737.8	NP_113606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO3	ENST00000256737.8 linkuse as main transcript	c.1290-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_031418.4	ENSP00000256737	P3	Q9BYT9-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

429

AN:

103988

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00339

Gnomad AMI

AF:

0.00192

Gnomad AMR

AF:

0.00198

Gnomad ASJ

AF:

0.00313

Gnomad EAS

AF:

0.00215

Gnomad SAS

AF:

0.00376

Gnomad FIN

AF:

0.00348

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00555

Gnomad OTH

AF:

0.00444

GnomAD3 exomes

AF:

0.0204

AC:

3078

AN:

150966

Hom.:

AF XY:

0.0213

AC XY:

1712

AN XY:

80428

show subpopulations

Gnomad AFR exome

AF:

0.0226

Gnomad AMR exome

AF:

0.00902

Gnomad ASJ exome

AF:

0.0376

Gnomad EAS exome

AF:

0.0100

Gnomad SAS exome

AF:

0.0364

Gnomad FIN exome

AF:

0.0269

Gnomad NFE exome

AF:

0.0198

Gnomad OTH exome

AF:

0.0201

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00838

AC:

7147

AN:

852534

Hom.:

Cov.:

AF XY:

0.00890

AC XY:

3809

AN XY:

427848

show subpopulations

Gnomad4 AFR exome

AF:

0.00939

Gnomad4 AMR exome

AF:

0.00860

Gnomad4 ASJ exome

AF:

0.0152

Gnomad4 EAS exome

AF:

0.00291

Gnomad4 SAS exome

AF:

0.0198

Gnomad4 FIN exome

AF:

0.0115

Gnomad4 NFE exome

AF:

0.00743

Gnomad4 OTH exome

AF:

0.00657

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00413

AC:

430

AN:

104030

Hom.:

Cov.:

AF XY:

0.00393

AC XY:

200

AN XY:

50910

show subpopulations

Gnomad4 AFR

AF:

0.00338

Gnomad4 AMR

AF:

0.00198

Gnomad4 ASJ

AF:

0.00313

Gnomad4 EAS

AF:

0.00215

Gnomad4 SAS

AF:

0.00377

Gnomad4 FIN

AF:

0.00348

Gnomad4 NFE

AF:

0.00555

Gnomad4 OTH

AF:

0.00512

Alfa

AF:

0.00784

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 26, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Dystonic disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.0

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000035

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.040

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