11-26332444-T-TAAA

Variant summary

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

The NM_031418.4(ANO3):c.46+137_46+139dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 603,458 control chromosomes in the GnomAD database, including 69 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0094 (20 hom., cov: 0)
  • Exomes 𝑓: 0.060 (49 hom.)
• Consequence: ANO3 NM_031418.4 intron
• Clinical Significance: Likely 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-TAAA is Benign according to our data. Variant chr11-26332444-T-TAAA is described in ClinVar as [Likely_benign]. Clinvar id is 1206545.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO3	NM_031418.4	c.46+137_46+139dup		intron_variant		ENST00000256737.8
ANO3	NM_001313726.2	c.229+22739_229+22741dup		intron_variant
ANO3	XM_047427399.1	c.46+137_46+139dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO3	ENST00000256737.8	c.46+137_46+139dup		intron_variant		1	NM_031418.4	P3
ANO3	ENST00000525139.5	c.-3+22739_-3+22741dup		intron_variant		5
ANO3	ENST00000531646.1	c.46+137_46+139dup		intron_variant		4
ANO3	ENST00000672621.1	c.229+22739_229+22741dup		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00930 AC: 1249 AN: 134268 Hom.: 20 Cov.: 0

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00418

Gnomad ASJ AF: 0.00272

Gnomad EAS AF: 0.00261

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.00793

Gnomad MID AF: 0.00333

Gnomad NFE AF: 0.00424

Gnomad OTH AF: 0.00841

GnomAD4 exome AF: 0.0595 AC: 27916 AN: 469156 Hom.: 49 AF XY: 0.0601 AC XY: 14826 AN XY: 246686

Gnomad4 AFR exome AF: 0.0416

Gnomad4 AMR exome AF: 0.0466

Gnomad4 ASJ exome AF: 0.0481

Gnomad4 EAS exome AF: 0.0299

Gnomad4 SAS exome AF: 0.0690

Gnomad4 FIN exome AF: 0.0798

Gnomad4 NFE exome AF: 0.0611

Gnomad4 OTH exome AF: 0.0571

GnomAD4 genome AF: 0.00936 AC: 1257 AN: 134302 Hom.: 20 Cov.: 0 AF XY: 0.00913 AC XY: 579 AN XY: 63386

Gnomad4 AFR AF: 0.0229

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.00272

Gnomad4 EAS AF: 0.00262

Gnomad4 SAS AF: 0.00413

Gnomad4 FIN AF: 0.00793

Gnomad4 NFE AF: 0.00424

Gnomad4 OTH AF: 0.00891

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 22, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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;