rs10834976

Variant names:

• chr11-26424644-G-A
• rs10834976
• NM_031418.4:c.47-17274G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-26424644-G-A
• chr11-26424644-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031418.4(ANO3):​c.47-17274G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 151,986 control chromosomes in the GnomAD database, including 49,008 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (49008 hom., cov: 31)
• Consequence: ANO3 NM_031418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• dystonia 24

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031418.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO3	NM_031418.4	MANE Select	c.47-17274G>A		intron	N/A	NP_113606.2
	ANO3	NM_001313726.2		c.230-17274G>A		intron	N/A	NP_001300655.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO3	ENST00000256737.8	TSL:1 MANE Select	c.47-17274G>A		intron	N/A	ENSP00000256737.3
	ANO3	ENST00000672621.1		c.230-17274G>A		intron	N/A	ENSP00000500506.1
	ANO3	ENST00000525139.5	TSL:5	c.-2-17274G>A		intron	N/A	ENSP00000432576.1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118975 AN: 151868 Hom.: 49002 Cov.: 31

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.941

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.823

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.783 AC: 119001 AN: 151986 Hom.: 49008 Cov.: 31 AF XY: 0.788 AC XY: 58584 AN XY: 74306

African (AFR) AF: 0.494 AC: 20470 AN: 41398

American (AMR) AF: 0.888 AC: 13520 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 3086 AN: 3472

East Asian (EAS) AF: 0.889 AC: 4585 AN: 5156

South Asian (SAS) AF: 0.941 AC: 4538 AN: 4824

European-Finnish (FIN) AF: 0.909 AC: 9643 AN: 10604

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60314 AN: 67988

Other (OTH) AF: 0.823 AC: 1734 AN: 2108

Alfa AF: 0.854 Hom.: 82567

Bravo AF: 0.768

Asia WGS AF: 0.898 AC: 3122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.40
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10834976; hg19: chr11-26446191;