11-26441920-A-G

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_031418.4(ANO3):c.49A>G(p.Met17Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000422 in 1,609,958 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

ANO3
NM_031418.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.43

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 66 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO3	NM_031418.4 link	c.49A>G	p.Met17Val	missense_variant, splice_region_variant	Exon 2 of 27	ENST00000256737.8	NP_113606.2	Q9BYT9-1
ANO3	NM_001313726.2 link	c.232A>G	p.Met78Val	missense_variant, splice_region_variant	Exon 3 of 28		NP_001300655.1	Q9BYT9A0A5F9ZHL6B7Z9B9
ANO3	XM_047427399.1 link	c.49A>G	p.Met17Val	missense_variant, splice_region_variant	Exon 2 of 26		XP_047283355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ANO3	ENST00000256737.8 link	c.49A>G	p.Met17Val	missense_variant, splice_region_variant	Exon 2 of 27	1	NM_031418.4	ENSP00000256737.3	Q9BYT9-1
ANO3	ENST00000672621.1 link	c.232A>G	p.Met78Val	missense_variant, splice_region_variant	Exon 3 of 28			ENSP00000500506.1	A0A5F9ZHL6
ANO3	ENST00000525139.5 link	c.1A>G	p.Met1?	start_lost, splice_region_variant	Exon 2 of 27	5		ENSP00000432576.1	E9PQ79
ANO3	ENST00000531646.1 link	c.49A>G	p.Met17Val	missense_variant, splice_region_variant	Exon 2 of 5	4		ENSP00000435275.1	E9PKW2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

247330

Hom.:

AF XY:

0.0000225

AC XY:

AN XY:

133600

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000357

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000453

AC:

AN:

1457770

Hom.:

Cov.:

AF XY:

0.0000414

AC XY:

AN XY:

725176

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000585

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000624

Hom.:

Bravo

AF:

0.0000113

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Feb 01, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.080

T;T;T

Eigen

Benign

-0.019

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.90

D;T;T

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.52

D;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.6

.;L;.

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.44

N;N;N

REVEL

Benign

0.21

Sift

Uncertain

0.011

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.0030

.;B;.

Vest4

0.92

MutPred

0.20

.;Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);

MVP

0.51

MPC

0.23

ClinPred

0.34

GERP RS

5.6

Varity_R

0.48

gMVP

0.48

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