Variant chr11-26537400-T-C 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.977-6T>C variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00006558

Clinical Significance

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

Conservation

PhyloP100: -0.106

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=-0.72).

BP6

Variant 11-26537400-T-C is Benign according to our data. Variant chr11-26537400-T-C is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	UniProt
ANO3	NM_031418.4 linkuse as main transcript	c.977-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000256737.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ANO3	ENST00000256737.8 linkuse as main transcript	c.977-6T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_031418.4	P3	Q9BYT9-1
ANO3	ENST00000525139.5 linkuse as main transcript	c.929-6T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5
ANO3	ENST00000531568.1 linkuse as main transcript	c.539-6T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2		A1	Q9BYT9-2
ANO3	ENST00000672621.1 linkuse as main transcript	c.1160-6T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

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

GnomAD3 exomes

AF:

0.0116

AC:

2914

AN:

251374

Hom.:

AF XY:

0.0103

AC XY:

1405

AN XY:

135860

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 SAS exome

AF:

0.00284

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

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0154

Gnomad4 ASJ exome

AF:

0.00345

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.00303

Gnomad4 FIN exome

AF:

0.0331

Gnomad4 NFE exome

AF:

0.000689

Gnomad4 OTH exome

AF:

0.00498

GnomAD4 genome

AF:

0.00785

AC:

1196

AN:

152314

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

793

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.0148

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.0793

Gnomad4 SAS

AF:

0.00372

Gnomad4 FIN

AF:

0.0403

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00268

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

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2018

- -

Dystonia 24

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Dystonic disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.77

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

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