rs2162321

Variant names:

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.382G>A(p.Ala128Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00655 in 1,613,824 control chromosomes in the GnomAD database, including 481 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 248 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 233 hom. )

Consequence

ANO6
NM_001025356.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.22

Publications

9 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 (MetaRNN=0.003555566).

BP6

Variant 12-45348064-G-A is Benign according to our data. Variant chr12-45348064-G-A is described in ClinVar as Benign. ClinVar VariationId is 257146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO6	NM_001025356.3 link	c.382G>A	p.Ala128Thr	missense_variant	Exon 5 of 20	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.382G>A	p.Ala128Thr	missense_variant	Exon 5 of 20	1	NM_001025356.3	ENSP00000320087.8		Q4KMQ2-1

Frequencies

GnomAD3 genomes

AF:

0.0324

AC:

4932

AN:

152012

Hom.:

245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0163

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00726

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0272

GnomAD2 exomes

AF:

0.00976

AC:

2451

AN:

251078

AF XY:

0.00734

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.00567

Gnomad ASJ exome

AF:

0.00854

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000256

Gnomad OTH exome

AF:

0.00441

GnomAD4 exome

AF:

0.00384

AC:

5618

AN:

1461694

Hom.:

233

Cov.:

AF XY:

0.00342

AC XY:

2489

AN XY:

727148

show subpopulations

African (AFR)

AF:

0.112

AC:

3744

AN:

33460

American (AMR)

AF:

0.00685

AC:

306

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00953

AC:

249

AN:

26130

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.00667

AC:

575

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00555

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000211

AC:

235

AN:

1111898

Other (OTH)

AF:

0.00788

AC:

476

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

277

554

832

1109

1386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

134

268

402

536

670

<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:

0.0325

AC:

4948

AN:

152130

Hom.:

248

Cov.:

AF XY:

0.0310

AC XY:

2309

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.110

AC:

4563

AN:

41482

American (AMR)

AF:

0.0162

AC:

248

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00727

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68012

Other (OTH)

AF:

0.0270

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

220

439

659

878

1098

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0132

Hom.:

200

Bravo

AF:

0.0374

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.112

AC:

495

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.0119

AC:

1446

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

.;.;T;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

D;D;D;D

MetaRNN

Benign

0.0036

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Pathogenic

3.1

M;.;M;.

PhyloP100

4.2

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.1

D;D;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.020

D;T;T;T

Sift4G

Benign

0.077

T;T;T;T

Polyphen

1.0

.;.;D;.

Vest4

0.29

MPC

0.38

ClinPred

0.044

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.16

gMVP

0.71

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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