11-26332096-T-A

Variant names:

• chr11-26332096-T-A
• rs1531394
• NM_001313726.2:c.229+22377T>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001313726.2(ANO3):​c.229+22377T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,468,950 control chromosomes in the GnomAD database, including 130,099 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10946 hom., cov: 31)
  • Exomes 𝑓: 0.42 (119153 hom.)
• Consequence: ANO3 NM_001313726.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.21
• Publications: 11 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-AS1 (HGNC:54190): (ANO3 antisense RNA 1)

LOC105376598 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 11-26332096-T-A is Benign according to our data. Variant chr11-26332096-T-A is described in ClinVar as Benign. ClinVar VariationId is 1247584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001313726.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO3	NM_001313726.2		c.229+22377T>A		intron	N/A	NP_001300655.1	A0A5F9ZHL6
	ANO3	NM_031418.4	MANE Select	c.-180T>A		upstream_gene	N/A	NP_113606.2	Q9BYT9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO3	ENST00000672621.1		c.229+22377T>A		intron	N/A	ENSP00000500506.1	A0A5F9ZHL6
	ANO3	ENST00000525139.5	TSL:5	c.-3+22377T>A		intron	N/A	ENSP00000432576.1	E9PQ79
	ANO3	ENST00000256737.8	TSL:1 MANE Select	c.-180T>A		upstream_gene	N/A	ENSP00000256737.3	Q9BYT9-1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52943 AN: 151944 Hom.: 10936 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.421 AC: 554061 AN: 1316888 Hom.: 119153 Cov.: 29 AF XY: 0.422 AC XY: 271372 AN XY: 643034

African (AFR) AF: 0.0969 AC: 2836 AN: 29282

American (AMR) AF: 0.564 AC: 14651 AN: 25958

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 10010 AN: 19744

East Asian (EAS) AF: 0.507 AC: 17825 AN: 35192

South Asian (SAS) AF: 0.457 AC: 30715 AN: 67166

European-Finnish (FIN) AF: 0.372 AC: 13366 AN: 35974

Middle Eastern (MID) AF: 0.424 AC: 1555 AN: 3664

European-Non Finnish (NFE) AF: 0.421 AC: 440340 AN: 1045334

Other (OTH) AF: 0.417 AC: 22763 AN: 54574

GnomAD4 genome AF: 0.348 AC: 52967 AN: 152062 Hom.: 10946 Cov.: 31 AF XY: 0.352 AC XY: 26120 AN XY: 74304

African (AFR) AF: 0.112 AC: 4635 AN: 41504

American (AMR) AF: 0.497 AC: 7596 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1812 AN: 3470

East Asian (EAS) AF: 0.464 AC: 2384 AN: 5134

South Asian (SAS) AF: 0.468 AC: 2251 AN: 4812

European-Finnish (FIN) AF: 0.373 AC: 3948 AN: 10586

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 29014 AN: 67958

Other (OTH) AF: 0.387 AC: 813 AN: 2102

Alfa AF: 0.380 Hom.: 1604

Bravo AF: 0.347

Asia WGS AF: 0.454 AC: 1579 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		2.2
PromoterAI		0.00070	Neutral
Mutation Taster		=300/0	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: rs1531394; hg19: chr11-26353643;