11-26332096-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 2.21

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]

ACMG classification

Verdict is Benign. Variant got -12 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 id is 1247584.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO3	NM_001313726.2	c.229+22377T>A		intron_variant
ANO3	NM_031418.4			upstream_gene_variant		ENST00000256737.8
ANO3	XM_047427399.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO3	ENST00000525139.5	c.-3+22377T>A		intron_variant		5
ANO3	ENST00000672621.1	c.229+22377T>A		intron_variant
ANO3	ENST00000256737.8			upstream_gene_variant		1	NM_031418.4	P3
ANO3	ENST00000531646.1			upstream_gene_variant		4

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

Gnomad4 AFR exome AF: 0.0969

Gnomad4 AMR exome AF: 0.564

Gnomad4 ASJ exome AF: 0.507

Gnomad4 EAS exome AF: 0.507

Gnomad4 SAS exome AF: 0.457

Gnomad4 FIN exome AF: 0.372

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.417

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

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.387

Alfa AF: 0.380 Hom.: 1604

Bravo AF: 0.347

Asia WGS AF: 0.454 AC: 1579 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 30, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	13
Dann	Benign	0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs1531394; hg19: chr11-26353643;