12-45328439-T-C

Position:

• chr12-45328439-T-C

Variant summary

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

The NM_001025356.3(ANO6):​c.151-2856T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,904 control chromosomes in the GnomAD database, including 20,514 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 0.51 (20514 hom., cov: 31)
• Consequence: ANO6 NM_001025356.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO6	NM_001025356.3	c.151-2856T>C		intron_variant		ENST00000320560.13	NP_001020527.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO6	ENST00000320560.13	c.151-2856T>C		intron_variant		1	NM_001025356.3	ENSP00000320087.8

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76974 AN: 151784 Hom.: 20484 Cov.: 31

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.507 AC: 77057 AN: 151904 Hom.: 20514 Cov.: 31 AF XY: 0.512 AC XY: 38031 AN XY: 74246

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.486

Alfa AF: 0.444 Hom.: 7752

Bravo AF: 0.503

Asia WGS AF: 0.558 AC: 1941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.1
DANN	Benign	0.47

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: rs965125; hg19: chr12-45722222;