11-26575451-G-A

Variant names:

• chr11-26575451-G-A
• rs11029621
• NM_031418.4:c.1447+15672G>A

Variant summary

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

The NM_031418.4(ANO3):​c.1447+15672G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,700 control chromosomes in the GnomAD database, including 18,252 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 0.49 (18252 hom., cov: 32)
• Consequence: ANO3 NM_031418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.832
• Publications: 1 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 (SAS) allele frequency at 95% confidence interval = 0.609 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.1447+15672G>A		intron	N/A	NP_113606.2
	ANO3	NM_001313726.2		c.1630+15672G>A		intron	N/A	NP_001300655.1
	ANO3	NM_001313727.2		c.1009+15672G>A		intron	N/A	NP_001300656.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO3	ENST00000256737.8	TSL:1 MANE Select	c.1447+15672G>A		intron	N/A	ENSP00000256737.3
	ANO3	ENST00000672621.1		c.1630+15672G>A		intron	N/A	ENSP00000500506.1
	ANO3	ENST00000525139.5	TSL:5	c.1399+15672G>A		intron	N/A	ENSP00000432576.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74121 AN: 151578 Hom.: 18243 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.489 AC: 74156 AN: 151700 Hom.: 18252 Cov.: 32 AF XY: 0.491 AC XY: 36421 AN XY: 74120

African (AFR) AF: 0.483 AC: 20022 AN: 41422

American (AMR) AF: 0.394 AC: 5998 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1917 AN: 3470

East Asian (EAS) AF: 0.511 AC: 2632 AN: 5146

South Asian (SAS) AF: 0.628 AC: 3017 AN: 4804

European-Finnish (FIN) AF: 0.504 AC: 5287 AN: 10482

Middle Eastern (MID) AF: 0.514 AC: 146 AN: 284

European-Non Finnish (NFE) AF: 0.495 AC: 33606 AN: 67842

Other (OTH) AF: 0.476 AC: 999 AN: 2100

Alfa AF: 0.497 Hom.: 2420

Bravo AF: 0.473

Asia WGS AF: 0.526 AC: 1774 AN: 3370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.6
DANN	Benign	0.36
PhyloP100		0.83
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: rs11029621; hg19: chr11-26596998;