12-45216643-C-T

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.70+252C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0586 in 152,262 control chromosomes in the GnomAD database, including 490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.059 (490 hom., cov: 32)
• Consequence: ANO6 NM_001025356.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.131

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=-0.78).
• BP6: Variant 12-45216643-C-T is Benign according to our data. Variant chr12-45216643-C-T is described in ClinVar as [Benign]. Clinvar id is 1287551.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO6	NM_001025356.3	c.70+252C>T		intron_variant		ENST00000320560.13
ANO6	NM_001142679.2	c.70+252C>T		intron_variant
ANO6	NM_001204803.2	c.70+252C>T		intron_variant
ANO6	XM_005268707.5	c.51+252C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO6	ENST00000320560.13	c.70+252C>T		intron_variant		1	NM_001025356.3	P4

Frequencies

GnomAD3 genomes AF: 0.0586 AC: 8917 AN: 152146 Hom.: 487 Cov.: 32

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0596

Gnomad OTH AF: 0.0564

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

GnomAD4 genome AF: 0.0586 AC: 8929 AN: 152262 Hom.: 490 Cov.: 32 AF XY: 0.0627 AC XY: 4665 AN XY: 74448

Gnomad4 AFR AF: 0.0187

Gnomad4 AMR AF: 0.0481

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.0704

Gnomad4 NFE AF: 0.0596

Gnomad4 OTH AF: 0.0629

Alfa AF: 0.0512 Hom.: 33

Bravo AF: 0.0543

Asia WGS AF: 0.201 AC: 697 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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	4.9
Dann	Benign	0.64

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: rs11612203; hg19: chr12-45610426;