11-26332014-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001313726.2(ANO3):c.229+22295T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,027,362 control chromosomes in the GnomAD database, including 508,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.98 (73118 hom., cov: 34)
  • Exomes 𝑓: 1.0 (435625 hom.)
• Consequence: ANO3 NM_001313726.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.382

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]

LOC105376598 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 11-26332014-T-C is Benign according to our data. Variant chr11-26332014-T-C is described in ClinVar as [Benign]. Clinvar id is 1288620.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO3	NM_001313726.2	c.229+22295T>C		intron_variant
LOC105376598	XR_931138.3			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO3	ENST00000525139.5	c.-3+22295T>C		intron_variant		5
ANO3	ENST00000672621.1	c.229+22295T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.979 AC: 149052 AN: 152204 Hom.: 73061 Cov.: 34

Gnomad AFR AF: 0.929

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.991

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.985

GnomAD4 exome AF: 0.998 AC: 873078 AN: 875040 Hom.: 435625 Cov.: 11 AF XY: 0.998 AC XY: 435679 AN XY: 436556

Gnomad4 AFR exome AF: 0.930

Gnomad4 AMR exome AF: 0.995

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.995

GnomAD4 genome AF: 0.979 AC: 149168 AN: 152322 Hom.: 73118 Cov.: 34 AF XY: 0.980 AC XY: 72983 AN XY: 74472

Gnomad4 AFR AF: 0.929

Gnomad4 AMR AF: 0.991

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.985

Alfa AF: 0.997 Hom.: 3321

Bravo AF: 0.978

Asia WGS AF: 0.996 AC: 3464 AN: 3478

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

Jul 05, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	18
Dann	Benign	0.92

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: rs1531395; hg19: chr11-26353561;