Variant 11-26332264-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_031418.4(ANO3):c.-12C>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 0.0281 in 1,613,902 control chromosomes in the GnomAD database, including 831 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.025 ( 67 hom., cov: 30)

Exomes 𝑓: 0.028 ( 764 hom. )

Consequence

ANO3
NM_031418.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.344

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=-0.49).

BP6

Variant 11-26332264-C-T is Benign according to our data. Variant chr11-26332264-C-T is described in ClinVar as [Benign]. Clinvar id is 1259186.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ANO3	NM_031418.4 linkuse as main transcript	c.-12C>T	5_prime_UTR_variant	1/27	ENST00000256737.8
ANO3	XM_047427399.1 linkuse as main transcript	c.-12C>T	5_prime_UTR_variant	1/26
ANO3	NM_001313726.2 linkuse as main transcript	c.229+22545C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO3	ENST00000256737.8 linkuse as main transcript	c.-12C>T	5_prime_UTR_variant	1/27	1	NM_031418.4	P3	Q9BYT9-1
ANO3	ENST00000531646.1 linkuse as main transcript	c.-12C>T	5_prime_UTR_variant	1/5	4
ANO3	ENST00000525139.5 linkuse as main transcript	c.-3+22545C>T	intron_variant		5
ANO3	ENST00000672621.1 linkuse as main transcript	c.229+22545C>T	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0248

AC:

3762

AN:

151924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00515

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0414

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00229

Gnomad FIN

AF:

0.0720

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0305

Gnomad OTH

AF:

0.0192

GnomAD3 exomes

AF:

0.0298

AC:

7490

AN:

251460

Hom.:

213

AF XY:

0.0269

AC XY:

3660

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00468

Gnomad AMR exome

AF:

0.0744

Gnomad ASJ exome

AF:

0.00318

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00193

Gnomad FIN exome

AF:

0.0673

Gnomad NFE exome

AF:

0.0277

Gnomad OTH exome

AF:

0.0235

GnomAD4 exome

AF:

0.0285

AC:

41601

AN:

1461860

Hom.:

764

Cov.:

AF XY:

0.0274

AC XY:

19911

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00370

Gnomad4 AMR exome

AF:

0.0686

Gnomad4 ASJ exome

AF:

0.00329

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00201

Gnomad4 FIN exome

AF:

0.0628

Gnomad4 NFE exome

AF:

0.0301

Gnomad4 OTH exome

AF:

0.0215

GnomAD4 genome

AF:

0.0248

AC:

3764

AN:

152042

Hom.:

Cov.:

AF XY:

0.0263

AC XY:

1954

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00513

Gnomad4 AMR

AF:

0.0416

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00229

Gnomad4 FIN

AF:

0.0720

Gnomad4 NFE

AF:

0.0305

Gnomad4 OTH

AF:

0.0190

Alfa

AF:

0.0286

Hom.:

Bravo

AF:

0.0220

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

Cadd

Benign

Dann

Benign

0.90

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