11-26332444-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_031418.4(ANO3):c.46+139dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 610,070 control chromosomes in the GnomAD database, including 14,240 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (13672 hom., cov: 0)
  • Exomes 𝑓: 0.32 (568 hom.)
• Consequence: ANO3 NM_031418.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.99

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 -10 ACMG points.

• BP6: Variant 11-26332444-T-TA is Benign according to our data. Variant chr11-26332444-T-TA is described in ClinVar as [Benign]. Clinvar id is 1273464.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO3	NM_031418.4	c.46+139dup		intron_variant		ENST00000256737.8
ANO3	NM_001313726.2	c.229+22741dup		intron_variant
ANO3	XM_047427399.1	c.46+139dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO3	ENST00000256737.8	c.46+139dup		intron_variant		1	NM_031418.4	P3
ANO3	ENST00000525139.5	c.-3+22741dup		intron_variant		5
ANO3	ENST00000531646.1	c.46+139dup		intron_variant		4
ANO3	ENST00000672621.1	c.229+22741dup		intron_variant

Frequencies

GnomAD3 genomes AF: 0.426 AC: 57216 AN: 134212 Hom.: 13669 Cov.: 0

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.537

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.453

GnomAD4 exome AF: 0.321 AC: 152959 AN: 475822 Hom.: 568 AF XY: 0.321 AC XY: 80379 AN XY: 250212

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.348

Gnomad4 ASJ exome AF: 0.361

Gnomad4 EAS exome AF: 0.331

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.426 AC: 57223 AN: 134248 Hom.: 13672 Cov.: 0 AF XY: 0.427 AC XY: 27064 AN XY: 63358

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.455

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

Sep 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs56225203; hg19: chr11-26353991;