chr11-26189234-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001313726.2(ANO3):c.58C>T(p.His20Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 984,950 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.010 ( 10 hom., cov: 32)

Exomes 𝑓: 0.014 ( 76 hom. )

Consequence

ANO3
NM_001313726.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.248

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 11-26189234-C-T is Benign according to our data. Variant chr11-26189234-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 3362365.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0103 (1571/152236) while in subpopulation SAS AF= 0.0168 (81/4828). AF 95% confidence interval is 0.0138. There are 10 homozygotes in gnomad4. There are 796 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1571 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO3	NM_001313726.2 link	c.58C>T	p.His20Tyr	missense_variant	Exon 1 of 28		NP_001300655.1	Q9BYT9A0A5F9ZHL6B7Z9B9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO3	ENST00000672621.1 link	c.58C>T	p.His20Tyr	missense_variant	Exon 1 of 28			ENSP00000500506.1		A0A5F9ZHL6
ANO3	ENST00000531798.1 link	n.112C>T		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1571

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00241

Gnomad AMI

AF:

0.0209

Gnomad AMR

AF:

0.00833

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0146

Gnomad OTH

AF:

0.0124

GnomAD4 exome

AF:

0.0137

AC:

11377

AN:

832714

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

5303

AN XY:

384546

show subpopulations

Gnomad4 AFR exome

AF:

0.00190

Gnomad4 AMR exome

AF:

0.00610

Gnomad4 ASJ exome

AF:

0.0444

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0161

Gnomad4 FIN exome

AF:

0.00725

Gnomad4 NFE exome

AF:

0.0137

Gnomad4 OTH exome

AF:

0.0140

GnomAD4 genome

AF:

0.0103

AC:

1571

AN:

152236

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

796

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00241

Gnomad4 AMR

AF:

0.00832

Gnomad4 ASJ

AF:

0.0294

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0168

Gnomad4 FIN

AF:

0.0115

Gnomad4 NFE

AF:

0.0145

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0103

Hom.:

Bravo

AF:

0.00957

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Dystonia 24

Uncertain:1

May 20, 2023

Neuberg Centre For Genomic Medicine, NCGM

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The observed missense c.58C>T (p.His20Tyr) variant in ANO3 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.His20Tyr variant is absent in gnomAD Exomes. This variant has not been submitted to the ClinVar database. The amino acid His at position 20 is changed to a Tyr changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS). -

not provided

Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ANO3: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.9

DANN

Benign

0.71

Splicing

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