Variant 12-45302107-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001025356.3(ANO6):c.150+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 1,610,344 control chromosomes in the GnomAD database, including 641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 42 hom., cov: 33)

Exomes 𝑓: 0.026 ( 599 hom. )

Consequence

ANO6
NM_001025356.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.306

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=-0.84).

BP6

Variant 12-45302107-C-T is Benign according to our data. Variant chr12-45302107-C-T is described in ClinVar as [Benign]. Clinvar id is 257141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-45302107-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0197 (2995/152274) while in subpopulation NFE AF= 0.0308 (2097/68010). AF 95% confidence interval is 0.0297. There are 42 homozygotes in gnomad4. There are 1435 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO6	NM_001025356.3 linkuse as main transcript	c.150+14C>T		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.150+14C>T		intron_variant		1	NM_001025356.3	ENSP00000320087	P4	Q4KMQ2-1

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

2995

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00471

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0178

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.0234

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0308

Gnomad OTH

AF:

0.0263

GnomAD3 exomes

AF:

0.0191

AC:

4785

AN:

251048

Hom.:

AF XY:

0.0192

AC XY:

2602

AN XY:

135666

show subpopulations

Gnomad AFR exome

AF:

0.00412

Gnomad AMR exome

AF:

0.0135

Gnomad ASJ exome

AF:

0.00953

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00539

Gnomad FIN exome

AF:

0.0277

Gnomad NFE exome

AF:

0.0286

Gnomad OTH exome

AF:

0.0237

GnomAD4 exome

AF:

0.0256

AC:

37382

AN:

1458070

Hom.:

599

Cov.:

AF XY:

0.0251

AC XY:

18217

AN XY:

725624

show subpopulations

Gnomad4 AFR exome

AF:

0.00381

Gnomad4 AMR exome

AF:

0.0143

Gnomad4 ASJ exome

AF:

0.0106

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00576

Gnomad4 FIN exome

AF:

0.0290

Gnomad4 NFE exome

AF:

0.0295

Gnomad4 OTH exome

AF:

0.0236

GnomAD4 genome

AF:

0.0197

AC:

2995

AN:

152274

Hom.:

Cov.:

AF XY:

0.0193

AC XY:

1435

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00469

Gnomad4 AMR

AF:

0.0177

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.0234

Gnomad4 NFE

AF:

0.0308

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.0230

Hom.:

Bravo

AF:

0.0183

Asia WGS

AF:

0.00289

AC:

AN:

3478

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.84

CADD

Benign

1.3

DANN

Benign

0.72

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