11-26332444-T-TAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_031418.4(ANO3):c.46+138_46+139dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0331 in 609,230 control chromosomes in the GnomAD database, including 39 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (27 hom., cov: 0)
  • Exomes 𝑓: 0.039 (12 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-TAA is Benign according to our data. Variant chr11-26332444-T-TAA is described in ClinVar as [Likely_benign]. Clinvar id is 1215038.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1672/134312) while in subpopulation AFR AF= 0.0286 (1031/35994). AF 95% confidence interval is 0.0272. There are 27 homozygotes in gnomad4. There are 854 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd at 1665 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO3	NM_031418.4	c.46+138_46+139dup		intron_variant		ENST00000256737.8
ANO3	NM_001313726.2	c.229+22740_229+22741dup		intron_variant
ANO3	XM_047427399.1	c.46+138_46+139dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO3	ENST00000256737.8	c.46+138_46+139dup		intron_variant		1	NM_031418.4	P3
ANO3	ENST00000525139.5	c.-3+22740_-3+22741dup		intron_variant		5
ANO3	ENST00000531646.1	c.46+138_46+139dup		intron_variant		4
ANO3	ENST00000672621.1	c.229+22740_229+22741dup		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1665 AN: 134280 Hom.: 26 Cov.: 0

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.0114

Gnomad AMR AF: 0.0161

Gnomad ASJ AF: 0.00665

Gnomad EAS AF: 0.00195

Gnomad SAS AF: 0.00358

Gnomad FIN AF: 0.00620

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00505

Gnomad OTH AF: 0.0112

GnomAD4 exome AF: 0.0390 AC: 18521 AN: 474918 Hom.: 12 AF XY: 0.0393 AC XY: 9815 AN XY: 249784

Gnomad4 AFR exome AF: 0.0361

Gnomad4 AMR exome AF: 0.0426

Gnomad4 ASJ exome AF: 0.0366

Gnomad4 EAS exome AF: 0.0226

Gnomad4 SAS exome AF: 0.0449

Gnomad4 FIN exome AF: 0.0410

Gnomad4 NFE exome AF: 0.0396

Gnomad4 OTH exome AF: 0.0393

GnomAD4 genome AF: 0.0124 AC: 1672 AN: 134312 Hom.: 27 Cov.: 0 AF XY: 0.0135 AC XY: 854 AN XY: 63372

Gnomad4 AFR AF: 0.0286

Gnomad4 AMR AF: 0.0160

Gnomad4 ASJ AF: 0.00665

Gnomad4 EAS AF: 0.00196

Gnomad4 SAS AF: 0.00335

Gnomad4 FIN AF: 0.00620

Gnomad4 NFE AF: 0.00505

Gnomad4 OTH AF: 0.0111

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

Sep 08, 2020

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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;