11-26332444-TA-T

Variant summary

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

The NM_031418.4(ANO3):c.46+139del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0665 in 607,514 control chromosomes in the GnomAD database, including 536 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.055 (527 hom., cov: 0)
  • Exomes 𝑓: 0.070 (9 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-TA-T is Benign according to our data. Variant chr11-26332444-TA-T is described in ClinVar as [Benign]. Clinvar id is 1271238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0555 AC: 7451 AN: 134248 Hom.: 528 Cov.: 0

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0237

Gnomad ASJ AF: 0.0194

Gnomad EAS AF: 0.00282

Gnomad SAS AF: 0.00256

Gnomad FIN AF: 0.00677

Gnomad MID AF: 0.00667

Gnomad NFE AF: 0.00679

Gnomad OTH AF: 0.0449

GnomAD4 exome AF: 0.0696 AC: 32933 AN: 473236 Hom.: 9 AF XY: 0.0686 AC XY: 17085 AN XY: 248988

Gnomad4 AFR exome AF: 0.242

Gnomad4 AMR exome AF: 0.0761

Gnomad4 ASJ exome AF: 0.0698

Gnomad4 EAS exome AF: 0.0909

Gnomad4 SAS exome AF: 0.0689

Gnomad4 FIN exome AF: 0.0574

Gnomad4 NFE exome AF: 0.0609

Gnomad4 OTH exome AF: 0.0778

GnomAD4 genome AF: 0.0555 AC: 7451 AN: 134278 Hom.: 527 Cov.: 0 AF XY: 0.0557 AC XY: 3526 AN XY: 63360

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.0237

Gnomad4 ASJ AF: 0.0194

Gnomad4 EAS AF: 0.00283

Gnomad4 SAS AF: 0.00206

Gnomad4 FIN AF: 0.00677

Gnomad4 NFE AF: 0.00679

Gnomad4 OTH AF: 0.0440

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

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;