Variant 11-26332444-TAAA-TAAAAAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_031418.4(ANO3):c.46+134_46+139dupAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000261 in 615,832 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000074 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

ANO3
NM_031418.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.99

Variant links:

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]

ANO3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000332 (160/481496) while in subpopulation AMR AF= 0.000674 (12/17796). AF 95% confidence interval is 0.000389. There are 0 homozygotes in gnomad4_exome. There are 83 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 160 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ANO3	NM_031418.4 link	c.46+134_46+139dupAAAAAA	intron_variant	Intron 1 of 26	ENST00000256737.8	NP_113606.2	Q9BYT9-1
ANO3	NM_001313726.2 link	c.229+22736_229+22741dupAAAAAA	intron_variant	Intron 2 of 27		NP_001300655.1	Q9BYT9A0A5F9ZHL6B7Z9B9
ANO3	XM_047427399.1 link	c.46+134_46+139dupAAAAAA	intron_variant	Intron 1 of 25		XP_047283355.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ANO3	ENST00000256737.8 link	c.46+123_46+124insAAAAAA	intron_variant	Intron 1 of 26	1	NM_031418.4	ENSP00000256737.3	Q9BYT9-1
ANO3	ENST00000672621.1 link	c.229+22725_229+22726insAAAAAA	intron_variant	Intron 2 of 27			ENSP00000500506.1	A0A5F9ZHL6
ANO3	ENST00000525139.5 link	c.-3+22725_-3+22726insAAAAAA	intron_variant	Intron 1 of 26	5		ENSP00000432576.1	E9PQ79
ANO3	ENST00000531646.1 link	c.46+123_46+124insAAAAAA	intron_variant	Intron 1 of 4	4		ENSP00000435275.1	E9PKW2

Frequencies

GnomAD3 genomes

AF:

0.00000744

AC:

AN:

134336

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000156

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000332

AC:

160

AN:

481496

Hom.:

AF XY:

0.000328

AC XY:

AN XY:

253272

show subpopulations

Gnomad4 AFR exome

AF:

0.000157

Gnomad4 AMR exome

AF:

0.000674

Gnomad4 ASJ exome

AF:

0.000152

Gnomad4 EAS exome

AF:

0.0000701

Gnomad4 SAS exome

AF:

0.000401

Gnomad4 FIN exome

AF:

0.000254

Gnomad4 NFE exome

AF:

0.000358

Gnomad4 OTH exome

AF:

0.000269

GnomAD4 genome

AF:

0.00000744

AC:

AN:

134336

Hom.:

Cov.:

AF XY:

0.0000158

AC XY:

AN XY:

63350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000156

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over