Variant chr11-26332222-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_031418.4(ANO3):c.-54C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,613,998 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0071 ( 10 hom., cov: 30)

Exomes 𝑓: 0.00076 ( 10 hom. )

Consequence

ANO3
NM_031418.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.55

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 11-26332222-C-T is Benign according to our data. Variant chr11-26332222-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1191751.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00707 (1076/152214) while in subpopulation AFR AF= 0.0242 (1007/41530). AF 95% confidence interval is 0.023. There are 10 homozygotes in gnomad4. There are 511 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1076 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ANO3	NM_031418.4 linkuse as main transcript	c.-54C>T	5_prime_UTR_variant	1/27	ENST00000256737.8
ANO3	XM_047427399.1 linkuse as main transcript	c.-54C>T	5_prime_UTR_variant	1/26
ANO3	NM_001313726.2 linkuse as main transcript	c.229+22503C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO3	ENST00000256737.8 linkuse as main transcript	c.-54C>T	5_prime_UTR_variant	1/27	1	NM_031418.4	P3	Q9BYT9-1
ANO3	ENST00000531646.1 linkuse as main transcript	c.-54C>T	5_prime_UTR_variant	1/5	4
ANO3	ENST00000525139.5 linkuse as main transcript	c.-3+22503C>T	intron_variant		5
ANO3	ENST00000672621.1 linkuse as main transcript	c.229+22503C>T	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00707

AC:

1076

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00526

GnomAD4 exome

AF:

0.000761

AC:

1113

AN:

1461784

Hom.:

Cov.:

AF XY:

0.000652

AC XY:

474

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.0247

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000908

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.00707

AC:

1076

AN:

152214

Hom.:

Cov.:

AF XY:

0.00687

AC XY:

511

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0242

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00571

Hom.:

Bravo

AF:

0.00798

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 03, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.88

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over