12-45293197-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001025356.3(ANO6):c.71-8817A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 152,180 control chromosomes in the GnomAD database, including 56,411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.85 (56411 hom., cov: 32)
• Consequence: ANO6 NM_001025356.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.965

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 12-45293197-A-C is Benign according to our data. Variant chr12-45293197-A-C is described in ClinVar as [Benign]. Clinvar id is 1253693.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO6	NM_001025356.3	c.71-8817A>C		intron_variant		ENST00000320560.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO6	ENST00000320560.13	c.71-8817A>C		intron_variant		1	NM_001025356.3	P4

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129906 AN: 152062 Hom.: 56399 Cov.: 32

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.936

Gnomad OTH AF: 0.871

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.854 AC: 129963 AN: 152180 Hom.: 56411 Cov.: 32 AF XY: 0.849 AC XY: 63167 AN XY: 74398

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.882

Gnomad4 ASJ AF: 0.920

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.796

Gnomad4 FIN AF: 0.908

Gnomad4 NFE AF: 0.936

Gnomad4 OTH AF: 0.864

Alfa AF: 0.893 Hom.: 8920

Bravo AF: 0.849

Asia WGS AF: 0.697 AC: 2427 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	13
Dann	Benign	0.94

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

Other links and lift over

dbSNP: rs7307262; hg19: chr12-45686980;