12-45301952-C-A

Position:

• chr12-45301952-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001025356.3(ANO6):​c.71-62C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.986 in 1,412,840 control chromosomes in the GnomAD database, including 688,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (66832 hom., cov: 32)
  • Exomes 𝑓: 0.99 (621762 hom.)
• Consequence: ANO6 NM_001025356.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.783

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 12-45301952-C-A is Benign according to our data. Variant chr12-45301952-C-A is described in ClinVar as [Benign]. Clinvar id is 1263239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO6	NM_001025356.3	c.71-62C>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.71-62C>A		intron_variant		1	NM_001025356.3	ENSP00000320087	P4

Frequencies

GnomAD3 genomes AF: 0.931 AC: 141690 AN: 152134 Hom.: 66806 Cov.: 32

Gnomad AFR AF: 0.765

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.971

Gnomad ASJ AF: 0.982

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.944

GnomAD4 exome AF: 0.993 AC: 1251162 AN: 1260588 Hom.: 621762 AF XY: 0.994 AC XY: 633751 AN XY: 637842

Gnomad4 AFR exome AF: 0.763

Gnomad4 AMR exome AF: 0.983

Gnomad4 ASJ exome AF: 0.987

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.983

GnomAD4 genome AF: 0.931 AC: 141766 AN: 152252 Hom.: 66832 Cov.: 32 AF XY: 0.934 AC XY: 69498 AN XY: 74446

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.971

Gnomad4 ASJ AF: 0.982

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.945

Alfa AF: 0.980 Hom.: 9798

Bravo AF: 0.921

Asia WGS AF: 0.980 AC: 3409 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.94
CADD	Benign	0.17
DANN	Benign	0.50

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: rs4140756; hg19: chr12-45695735;