12-45331006-G-A

Position:

• chr12-45331006-G-A

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.151-289G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0686 in 151,574 control chromosomes in the GnomAD database, including 562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.069 (562 hom., cov: 31)
• Consequence: ANO6 NM_001025356.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.325

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=-0.87).
• BP6: Variant 12-45331006-G-A is Benign according to our data. Variant chr12-45331006-G-A is described in ClinVar as [Benign]. Clinvar id is 1290375.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO6	NM_001025356.3	c.151-289G>A		intron_variant		ENST00000320560.13	NP_001020527.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO6	ENST00000320560.13	c.151-289G>A		intron_variant		1	NM_001025356.3	ENSP00000320087	P4

Frequencies

GnomAD3 genomes AF: 0.0686 AC: 10385 AN: 151456 Hom.: 559 Cov.: 31

Gnomad AFR AF: 0.0718

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0465

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0922

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0470

Gnomad OTH AF: 0.0618

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

GnomAD4 genome AF: 0.0686 AC: 10402 AN: 151574 Hom.: 562 Cov.: 31 AF XY: 0.0734 AC XY: 5432 AN XY: 74014

Gnomad4 AFR AF: 0.0719

Gnomad4 AMR AF: 0.0470

Gnomad4 ASJ AF: 0.0424

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0922

Gnomad4 NFE AF: 0.0470

Gnomad4 OTH AF: 0.0678

Alfa AF: 0.0334 Hom.: 22

Bravo AF: 0.0648

Asia WGS AF: 0.214 AC: 741 AN: 3474

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	-0.87
CADD	Benign	0.29
DANN	Benign	0.68

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: rs11182983; hg19: chr12-45724789;