chr11-26241538-T-C

Variant names:

• chr11-26241538-T-C
• rs9332433
• NM_001313726.2:c.154+52208T>C

Variant summary

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

The NM_001313726.2(ANO3):​c.154+52208T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,970 control chromosomes in the GnomAD database, including 9,679 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 0.35 (9679 hom., cov: 32)
• Consequence: ANO3 NM_001313726.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO3	NM_001313726.2	c.154+52208T>C		intron_variant	Intron 1 of 27		NP_001300655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO3	ENST00000672621.1	c.154+52208T>C		intron_variant	Intron 1 of 27			ENSP00000500506.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53412 AN: 151852 Hom.: 9657 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.352 AC: 53482 AN: 151970 Hom.: 9679 Cov.: 32 AF XY: 0.354 AC XY: 26308 AN XY: 74284

African (AFR) AF: 0.364 AC: 15106 AN: 41452

American (AMR) AF: 0.298 AC: 4543 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1063 AN: 3468

East Asian (EAS) AF: 0.154 AC: 795 AN: 5174

South Asian (SAS) AF: 0.317 AC: 1524 AN: 4814

European-Finnish (FIN) AF: 0.465 AC: 4894 AN: 10536

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24475 AN: 67954

Other (OTH) AF: 0.318 AC: 669 AN: 2104

Alfa AF: 0.341 Hom.: 5014

Bravo AF: 0.342

Asia WGS AF: 0.265 AC: 921 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.54
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9332433; hg19: chr11-26263085;