11-26557946-C-T

Variant names:

• chr11-26557946-C-T
• rs293966
• NM_031418.4:c.1387-1773C>T

Variant summary

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

The NM_031418.4(ANO3):​c.1387-1773C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,202 control chromosomes in the GnomAD database, including 59,528 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 0.88 (59528 hom., cov: 32)
• Consequence: ANO3 NM_031418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO3	NM_031418.4	c.1387-1773C>T		intron_variant	Intron 13 of 26	ENST00000256737.8	NP_113606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO3	ENST00000256737.8	c.1387-1773C>T		intron_variant	Intron 13 of 26	1	NM_031418.4	ENSP00000256737.3

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133930 AN: 152084 Hom.: 59507 Cov.: 32

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.911

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.961

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.892

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

GnomAD4 genome AF: 0.880 AC: 133999 AN: 152202 Hom.: 59528 Cov.: 32 AF XY: 0.882 AC XY: 65587 AN XY: 74400

African (AFR) AF: 0.755 AC: 31328 AN: 41488

American (AMR) AF: 0.929 AC: 14198 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.911 AC: 3163 AN: 3472

East Asian (EAS) AF: 0.961 AC: 4970 AN: 5174

South Asian (SAS) AF: 0.868 AC: 4183 AN: 4820

European-Finnish (FIN) AF: 0.961 AC: 10212 AN: 10622

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.927 AC: 63025 AN: 68024

Other (OTH) AF: 0.886 AC: 1872 AN: 2114

Alfa AF: 0.908 Hom.: 77808

Bravo AF: 0.875

Asia WGS AF: 0.883 AC: 3073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.50
PhyloP100		-1.9
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: rs293966; hg19: chr11-26579493;