11-26553944-T-C

Variant names:

• chr11-26553944-T-C
• rs293969
• NM_031418.4:c.1386+599T>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.1386+599T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 152,082 control chromosomes in the GnomAD database, including 45,886 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 (45886 hom., cov: 32)
• Consequence: ANO3 NM_031418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO3	NM_031418.4	c.1386+599T>C		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.1386+599T>C		intron_variant	Intron 13 of 26	1	NM_031418.4	ENSP00000256737.3

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117879 AN: 151964 Hom.: 45865 Cov.: 32

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.776 AC: 117947 AN: 152082 Hom.: 45886 Cov.: 32 AF XY: 0.782 AC XY: 58109 AN XY: 74338

African (AFR) AF: 0.748 AC: 31019 AN: 41468

American (AMR) AF: 0.814 AC: 12416 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 2767 AN: 3468

East Asian (EAS) AF: 0.829 AC: 4281 AN: 5162

South Asian (SAS) AF: 0.793 AC: 3832 AN: 4830

European-Finnish (FIN) AF: 0.870 AC: 9219 AN: 10600

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51902 AN: 67986

Other (OTH) AF: 0.768 AC: 1624 AN: 2114

Alfa AF: 0.764 Hom.: 127818

Bravo AF: 0.770

Asia WGS AF: 0.787 AC: 2738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.91
DANN	Benign	0.28
PhyloP100		-0.81
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: rs293969; hg19: chr11-26575491;