11-26332444-T-TAAAA

Variant summary

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

The NM_031418.4(ANO3):c.46+136_46+139dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 596,948 control chromosomes in the GnomAD database, including 4,440 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (4326 hom., cov: 0)
  • Exomes 𝑓: 0.13 (114 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-TAAAA is Benign according to our data. Variant chr11-26332444-T-TAAAA is described in ClinVar as [Benign]. Clinvar id is 1225565.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO3	NM_031418.4	c.46+136_46+139dup		intron_variant		ENST00000256737.8
ANO3	NM_001313726.2	c.229+22738_229+22741dup		intron_variant
ANO3	XM_047427399.1	c.46+136_46+139dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO3	ENST00000256737.8	c.46+136_46+139dup		intron_variant		1	NM_031418.4	P3
ANO3	ENST00000525139.5	c.-3+22738_-3+22741dup		intron_variant		5
ANO3	ENST00000531646.1	c.46+136_46+139dup		intron_variant		4
ANO3	ENST00000672621.1	c.229+22738_229+22741dup		intron_variant

Frequencies

GnomAD3 genomes AF: 0.248 AC: 33101 AN: 133656 Hom.: 4331 Cov.: 0

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.270

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.126 AC: 58495 AN: 463260 Hom.: 114 AF XY: 0.127 AC XY: 30921 AN XY: 243456

Gnomad4 AFR exome AF: 0.0705

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.0995

Gnomad4 EAS exome AF: 0.0728

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.248 AC: 33091 AN: 133688 Hom.: 4326 Cov.: 0 AF XY: 0.244 AC XY: 15422 AN XY: 63086

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.236

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

Nov 14, 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;