12-45298676-C-T

Variant names:

• chr12-45298676-C-T
• rs4768600
• NM_001025356.3:c.71-3338C>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.71-3338C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 152,198 control chromosomes in the GnomAD database, including 61,845 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 0.89 (61845 hom., cov: 32)
• Consequence: ANO6 NM_001025356.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188
• Publications: 0 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

ENSG00000293678 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.981 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.71-3338C>T		intron	N/A	NP_001020527.2	Q4KMQ2-1
	ANO6	NM_001204803.2		c.134-3338C>T		intron	N/A	NP_001191732.1	Q4KMQ2-2
	ANO6	NM_001142679.2		c.71-3338C>T		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.71-3338C>T		intron	N/A	ENSP00000320087.8	Q4KMQ2-1
	ANO6	ENST00000423947.7	TSL:1	c.134-3338C>T		intron	N/A	ENSP00000409126.3	Q4KMQ2-2
	ANO6	ENST00000425752.6	TSL:1	c.71-3338C>T		intron	N/A	ENSP00000391417.2	Q4KMQ2-4

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135637 AN: 152080 Hom.: 61826 Cov.: 32

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.921

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.930

Gnomad FIN AF: 0.971

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.911

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

GnomAD4 genome AF: 0.892 AC: 135700 AN: 152198 Hom.: 61845 Cov.: 32 AF XY: 0.892 AC XY: 66355 AN XY: 74414

African (AFR) AF: 0.686 AC: 28438 AN: 41460

American (AMR) AF: 0.921 AC: 14087 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 3349 AN: 3472

East Asian (EAS) AF: 0.914 AC: 4731 AN: 5174

South Asian (SAS) AF: 0.930 AC: 4485 AN: 4822

European-Finnish (FIN) AF: 0.971 AC: 10316 AN: 10620

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.987 AC: 67169 AN: 68036

Other (OTH) AF: 0.911 AC: 1925 AN: 2112

Alfa AF: 0.923 Hom.: 8528

Bravo AF: 0.880

Asia WGS AF: 0.909 AC: 3159 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Benign	0.73
PhyloP100		0.19
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: rs4768600; hg19: chr12-45692459;