chr12-45381125-A-G

Position:

• chr12-45381125-A-G

Variant summary

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

The ENST00000320560.13(ANO6):​c.1165+3012A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 152,220 control chromosomes in the GnomAD database, including 769 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 0.080 (769 hom., cov: 32)
• Consequence: ANO6 ENST00000320560.13 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO6	NM_001025356.3	c.1165+3012A>G		intron_variant		ENST00000320560.13	NP_001020527.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO6	ENST00000320560.13	c.1165+3012A>G		intron_variant		1	NM_001025356.3	ENSP00000320087	P4

Frequencies

GnomAD3 genomes AF: 0.0795 AC: 12088 AN: 152102 Hom.: 763 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0725

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0990

Gnomad FIN AF: 0.0385

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0746

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

GnomAD4 genome AF: 0.0797 AC: 12125 AN: 152220 Hom.: 769 Cov.: 32 AF XY: 0.0812 AC XY: 6046 AN XY: 74430

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.0726

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.0999

Gnomad4 FIN AF: 0.0385

Gnomad4 NFE AF: 0.0302

Gnomad4 OTH AF: 0.0739

Alfa AF: 0.0412 Hom.: 224

Bravo AF: 0.0844

Asia WGS AF: 0.118 AC: 409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.0
DANN	Benign	0.57

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: rs17095830; hg19: chr12-45774908;