Variant 11-26332444-TAAA-TAAAAAAAA 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+135_46+139dupAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00772 in 613,326 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0047 ( 4 hom., cov: 0)

Exomes 𝑓: 0.0086 ( 1 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 allele frequency = 0.00469 (630/134336) while in subpopulation AMR AF= 0.00858 (107/12464). AF 95% confidence interval is 0.00727. There are 4 homozygotes in gnomad4. There are 300 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 630 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ANO3	NM_031418.4 link	c.46+135_46+139dupAAAAA	intron_variant	Intron 1 of 26	ENST00000256737.8	NP_113606.2	Q9BYT9-1
ANO3	NM_001313726.2 link	c.229+22737_229+22741dupAAAAA	intron_variant	Intron 2 of 27		NP_001300655.1	Q9BYT9A0A5F9ZHL6B7Z9B9
ANO3	XM_047427399.1 link	c.46+135_46+139dupAAAAA	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+124insAAAAA	intron_variant	Intron 1 of 26	1	NM_031418.4	ENSP00000256737.3	Q9BYT9-1
ANO3	ENST00000672621.1 link	c.229+22725_229+22726insAAAAA	intron_variant	Intron 2 of 27			ENSP00000500506.1	A0A5F9ZHL6
ANO3	ENST00000525139.5 link	c.-3+22725_-3+22726insAAAAA	intron_variant	Intron 1 of 26	5		ENSP00000432576.1	E9PQ79
ANO3	ENST00000531646.1 link	c.46+123_46+124insAAAAA	intron_variant	Intron 1 of 4	4		ENSP00000435275.1	E9PKW2

Frequencies

GnomAD3 genomes

AF:

0.00468

AC:

629

AN:

134302

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00303

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00859

Gnomad ASJ

AF:

0.00272

Gnomad EAS

AF:

0.00109

Gnomad SAS

AF:

0.00486

Gnomad FIN

AF:

0.00489

Gnomad MID

AF:

0.00667

Gnomad NFE

AF:

0.00517

Gnomad OTH

AF:

0.00673

GnomAD4 exome

AF:

0.00856

AC:

4102

AN:

478990

Hom.:

AF XY:

0.00869

AC XY:

2190

AN XY:

251918

show subpopulations

Gnomad4 AFR exome

AF:

0.00418

Gnomad4 AMR exome

AF:

0.00860

Gnomad4 ASJ exome

AF:

0.00558

Gnomad4 EAS exome

AF:

0.00334

Gnomad4 SAS exome

AF:

0.0124

Gnomad4 FIN exome

AF:

0.00745

Gnomad4 NFE exome

AF:

0.00893

Gnomad4 OTH exome

AF:

0.00906

GnomAD4 genome

AF:

0.00469

AC:

630

AN:

134336

Hom.:

Cov.:

AF XY:

0.00473

AC XY:

300

AN XY:

63396

show subpopulations

Gnomad4 AFR

AF:

0.00303

Gnomad4 AMR

AF:

0.00858

Gnomad4 ASJ

AF:

0.00272

Gnomad4 EAS

AF:

0.00109

Gnomad4 SAS

AF:

0.00516

Gnomad4 FIN

AF:

0.00489

Gnomad4 NFE

AF:

0.00517

Gnomad4 OTH

AF:

0.00669

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