chr12-45339639-C-T

Variant names:

• chr12-45339639-C-T
• rs12579771
• NM_001025356.3:c.280-7383C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• Scott syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000293678 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ANO6	NM_001025356.3	c.280-7383C>T		intron_variant	Intron 3 of 19	ENST00000320560.13	NP_001020527.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO6	ENST00000320560.13	c.280-7383C>T		intron_variant	Intron 3 of 19	1	NM_001025356.3	ENSP00000320087.8

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

African (AFR) AF: 0.0877 AC: 3638 AN: 41492

American (AMR) AF: 0.168 AC: 2558 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 667 AN: 3466

East Asian (EAS) AF: 0.309 AC: 1594 AN: 5158

South Asian (SAS) AF: 0.464 AC: 2237 AN: 4818

European-Finnish (FIN) AF: 0.241 AC: 2548 AN: 10558

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15292 AN: 67918

Other (OTH) AF: 0.217 AC: 457 AN: 2108

Alfa AF: 0.217 Hom.: 3534

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
PhyloP100		0.85
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12579771; hg19: chr12-45733422;