Variant chr12-45350652-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.748-7G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00738 in 1,610,230 control chromosomes in the GnomAD database, including 480 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 244 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 236 hom. )

Consequence

ANO6
NM_001025356.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001468

Clinical Significance

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

Conservation

PhyloP100: 1.52

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 12-45350652-G-A is Benign according to our data. Variant chr12-45350652-G-A is described in ClinVar as [Benign]. Clinvar id is 257147.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 linkuse as main transcript	c.748-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000320560.13	NP_001020527.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO6	ENST00000320560.13 linkuse as main transcript	c.748-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001025356.3	ENSP00000320087	P4	Q4KMQ2-1

Frequencies

GnomAD3 genomes

AF:

0.0329

AC:

4997

AN:

152092

Hom.:

241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0175

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00725

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.0278

GnomAD3 exomes

AF:

0.0103

AC:

2568

AN:

250526

Hom.:

113

AF XY:

0.00779

AC XY:

1055

AN XY:

135346

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.00612

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00712

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000997

Gnomad OTH exome

AF:

0.00507

GnomAD4 exome

AF:

0.00471

AC:

6864

AN:

1458020

Hom.:

236

Cov.:

AF XY:

0.00425

AC XY:

3083

AN XY:

725556

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.00730

Gnomad4 ASJ exome

AF:

0.0113

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00664

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00121

Gnomad4 OTH exome

AF:

0.00919

GnomAD4 genome

AF:

0.0330

AC:

5017

AN:

152210

Hom.:

244

Cov.:

AF XY:

0.0316

AC XY:

2352

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.0175

Gnomad4 ASJ

AF:

0.00836

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00725

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00116

Gnomad4 OTH

AF:

0.0275

Alfa

AF:

0.00773

Hom.:

Bravo

AF:

0.0381

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.000981

EpiControl

AF:

0.000950

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

BayesDel_noAF

Benign

-0.53

CADD

Benign

3.0

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000015

dbscSNV1_RF

Benign

0.0

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