Genetic Variant ANO6:c.1783-13T>C (chr12-45403426-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001025356.3(ANO6):c.1783-13T>C variant causes a intron change. The variant allele was found at a frequency of 0.0229 in 1,605,022 control chromosomes in the GnomAD database, including 695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 43 hom., cov: 32)

Exomes 𝑓: 0.024 ( 652 hom. )

Consequence

ANO6
NM_001025356.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.61

Publications

2 publications found

Variant links:

Genes affected

ANO6 (HGNC:25240): (anoctamin 6) This gene encodes a multi-pass transmembrane protein that belongs to the anoctamin family. This protein is an essential component for the calcium-dependent exposure of phosphatidylserine on the cell surface. The scrambling of phospholipid occurs in various biological systems, such as when blood platelets are activated, they expose phosphatidylserine to trigger the clotting system. Mutations in this gene are associated with Scott syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]

ANO6 Gene-Disease associations (from GenCC):

Scott syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ANO6 links:

ENSG00000293678 (HGNC:):

ENSG00000293678 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 12-45403426-T-C is Benign according to our data. Variant chr12-45403426-T-C is described in ClinVar as Benign. ClinVar VariationId is 257143.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO6	NM_001025356.3 link	c.1783-13T>C		intron_variant	Intron 14 of 19	ENST00000320560.13	NP_001020527.2	Q4KMQ2-1B3KX12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO6	ENST00000320560.13 link	c.1783-13T>C		intron_variant	Intron 14 of 19	1	NM_001025356.3	ENSP00000320087.8		Q4KMQ2-1

Frequencies

GnomAD3 genomes

AF:

0.0167

AC:

2549

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00292

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0728

Gnomad FIN

AF:

0.0230

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0222

Gnomad OTH

AF:

0.0163

GnomAD2 exomes

AF:

0.0251

AC:

6288

AN:

250856

AF XY:

0.0285

show subpopulations

Gnomad AFR exome

AF:

0.00278

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.0183

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0255

Gnomad NFE exome

AF:

0.0251

Gnomad OTH exome

AF:

0.0260

GnomAD4 exome

AF:

0.0235

AC:

34161

AN:

1452654

Hom.:

652

Cov.:

AF XY:

0.0253

AC XY:

18272

AN XY:

723316

show subpopulations

African (AFR)

AF:

0.00406

AC:

135

AN:

33260

American (AMR)

AF:

0.0105

AC:

469

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0177

AC:

461

AN:

26072

East Asian (EAS)

AF:

0.000227

AC:

AN:

39626

South Asian (SAS)

AF:

0.0698

AC:

6007

AN:

86048

European-Finnish (FIN)

AF:

0.0271

AC:

1444

AN:

53352

Middle Eastern (MID)

AF:

0.0517

AC:

297

AN:

5750

European-Non Finnish (NFE)

AF:

0.0218

AC:

24024

AN:

1103764

Other (OTH)

AF:

0.0219

AC:

1315

AN:

60068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1790

3580

5370

7160

8950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

908

1816

2724

3632

4540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0167

AC:

2552

AN:

152368

Hom.:

Cov.:

AF XY:

0.0173

AC XY:

1290

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.00293

AC:

122

AN:

41580

American (AMR)

AF:

0.0119

AC:

182

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0190

AC:

AN:

3472

East Asian (EAS)

AF:

0.000385

AC:

AN:

5196

South Asian (SAS)

AF:

0.0731

AC:

353

AN:

4830

European-Finnish (FIN)

AF:

0.0230

AC:

244

AN:

10624

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0223

AC:

1515

AN:

68038

Other (OTH)

AF:

0.0161

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

127

253

380

506

633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0219

Hom.:

Bravo

AF:

0.0146

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

3.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over