rs12579771

chr12-45339639-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001025356.3(ANO6):c.280-7383C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 151,972 control chromosomes in the GnomAD database, including 3,331 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3331 hom., cov: 32)
• Consequence: ANO6 NM_001025356.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.847

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO6	NM_001025356.3	c.280-7383C>T		intron_variant		ENST00000320560.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO6	ENST00000320560.13	c.280-7383C>T		intron_variant		1	NM_001025356.3	P4

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29208 AN: 151854 Hom.: 3336 Cov.: 32

Gnomad AFR AF: 0.0878

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.192 AC: 29197 AN: 151972 Hom.: 3331 Cov.: 32 AF XY: 0.196 AC XY: 14589 AN XY: 74288

Gnomad4 AFR AF: 0.0877

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.217

Alfa AF: 0.218 Hom.: 3094

Bravo AF: 0.176

Asia WGS AF: 0.330 AC: 1143 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	15
Dann	Benign	0.75

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: rs12579771; hg19: chr12-45733422;