Variant chr12-45348064-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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 (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
ANO6	NM_001025356.3 link	c.382G>A	p.Ala128Thr	missense_variant	5/20	ENST00000320560.13	NP_001020527.2	Q4KMQ2-1B3KX12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO6	ENST00000320560.13 link	c.382G>A	p.Ala128Thr	missense_variant	5/20	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

GnomAD3 exomes

AF:

0.00976

AC:

2451

AN:

251078

Hom.:

113

AF XY:

0.00734

AC XY:

996

AN XY:

135712

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 SAS exome

AF:

0.00722

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

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.00685

Gnomad4 ASJ exome

AF:

0.00953

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00667

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000211

Gnomad4 OTH exome

AF:

0.00788

GnomAD4 genome

AF:

0.0325

AC:

4948

AN:

152130

Hom.:

248

Cov.:

AF XY:

0.0310

AC XY:

2309

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.0162

Gnomad4 ASJ

AF:

0.00692

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00727

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.00782

Hom.:

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

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;.

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

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