chr12-45293197-A-C

Variant names:

• chr12-45293197-A-C
• rs7307262
• NM_001025356.3:c.71-8817A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001025356.3(ANO6):​c.71-8817A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 152,180 control chromosomes in the GnomAD database, including 56,411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.85 (56411 hom., cov: 32)
• Consequence: ANO6 NM_001025356.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.965
• Publications: 1 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 12-45293197-A-C is Benign according to our data. Variant chr12-45293197-A-C is described in ClinVar as Benign. ClinVar VariationId is 1253693.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025356.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO6	NM_001025356.3	MANE Select	c.71-8817A>C		intron	N/A	NP_001020527.2	Q4KMQ2-1
	ANO6	NM_001204803.2		c.134-8817A>C		intron	N/A	NP_001191732.1	Q4KMQ2-2
	ANO6	NM_001142679.2		c.71-8817A>C		intron	N/A	NP_001136151.1	Q4KMQ2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO6	ENST00000320560.13	TSL:1 MANE Select	c.71-8817A>C		intron	N/A	ENSP00000320087.8	Q4KMQ2-1
	ANO6	ENST00000423947.7	TSL:1	c.134-8817A>C		intron	N/A	ENSP00000409126.3	Q4KMQ2-2
	ANO6	ENST00000425752.6	TSL:1	c.71-8817A>C		intron	N/A	ENSP00000391417.2	Q4KMQ2-4

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129906 AN: 152062 Hom.: 56399 Cov.: 32

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.936

Gnomad OTH AF: 0.871

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

GnomAD4 genome AF: 0.854 AC: 129963 AN: 152180 Hom.: 56411 Cov.: 32 AF XY: 0.849 AC XY: 63167 AN XY: 74398

African (AFR) AF: 0.728 AC: 30209 AN: 41506

American (AMR) AF: 0.882 AC: 13488 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3193 AN: 3472

East Asian (EAS) AF: 0.570 AC: 2941 AN: 5164

South Asian (SAS) AF: 0.796 AC: 3842 AN: 4824

European-Finnish (FIN) AF: 0.908 AC: 9616 AN: 10590

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.936 AC: 63696 AN: 68020

Other (OTH) AF: 0.864 AC: 1822 AN: 2108

Alfa AF: 0.887 Hom.: 9109

Bravo AF: 0.849

Asia WGS AF: 0.697 AC: 2427 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.94
PhyloP100		0.96
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: rs7307262; hg19: chr12-45686980;