Variant 11-26441908-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_031418.4(ANO3):c.47-10G>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000689 in 1,602,040 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 1 hom. )

Consequence

ANO3
NM_031418.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001735

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.37

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 11-26441908-G-C is Benign according to our data. Variant chr11-26441908-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 526228.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-26441908-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000559 (85/152106) while in subpopulation AMR AF= 0.00105 (16/15276). AF 95% confidence interval is 0.000657. There are 0 homozygotes in gnomad4. There are 42 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 85 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ANO3	NM_031418.4 linkuse as main transcript	c.47-10G>C	splice_polypyrimidine_tract_variant, intron_variant	ENST00000256737.8
ANO3	NM_001313726.2 linkuse as main transcript	c.230-10G>C	splice_polypyrimidine_tract_variant, intron_variant
ANO3	XM_047427399.1 linkuse as main transcript	c.47-10G>C	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ANO3	ENST00000256737.8 linkuse as main transcript	c.47-10G>C	splice_polypyrimidine_tract_variant, intron_variant	1	NM_031418.4	P3	Q9BYT9-1
ANO3	ENST00000525139.5 linkuse as main transcript	c.-2-10G>C	splice_polypyrimidine_tract_variant, intron_variant	5
ANO3	ENST00000531646.1 linkuse as main transcript	c.47-10G>C	splice_polypyrimidine_tract_variant, intron_variant	4
ANO3	ENST00000672621.1 linkuse as main transcript	c.230-10G>C	splice_polypyrimidine_tract_variant, intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000559

AC:

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000457

AC:

111

AN:

243102

Hom.:

AF XY:

0.000419

AC XY:

AN XY:

131342

show subpopulations

Gnomad AFR exome

AF:

0.0000625

Gnomad AMR exome

AF:

0.000671

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000470

Gnomad NFE exome

AF:

0.000676

Gnomad OTH exome

AF:

0.000508

GnomAD4 exome

AF:

0.000703

AC:

1019

AN:

1449934

Hom.:

Cov.:

AF XY:

0.000674

AC XY:

486

AN XY:

721338

show subpopulations

Gnomad4 AFR exome

AF:

0.000244

Gnomad4 AMR exome

AF:

0.000561

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.000678

Gnomad4 NFE exome

AF:

0.000821

Gnomad4 OTH exome

AF:

0.000702

GnomAD4 genome

AF:

0.000559

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.000565

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000943

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000682

Hom.:

Bravo

AF:

0.000461

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Dystonic disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00017

dbscSNV1_RF

Benign

0.19

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