NM_001025356.3:c.151-2856T>C

Variant names:

• chr12-45328439-T-C
• rs965125
• NM_001025356.3:c.151-2856T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001025356.3(ANO6):​c.151-2856T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,904 control chromosomes in the GnomAD database, including 20,514 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 0.51 (20514 hom., cov: 31)
• Consequence: ANO6 NM_001025356.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 4 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 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.151-2856T>C		intron	N/A	NP_001020527.2	Q4KMQ2-1
	ANO6	NM_001204803.2		c.214-2856T>C		intron	N/A	NP_001191732.1	Q4KMQ2-2
	ANO6	NM_001142679.2		c.151-2856T>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.151-2856T>C		intron	N/A	ENSP00000320087.8	Q4KMQ2-1
	ANO6	ENST00000423947.7	TSL:1	c.214-2856T>C		intron	N/A	ENSP00000409126.3	Q4KMQ2-2
	ANO6	ENST00000425752.6	TSL:1	c.151-2856T>C		intron	N/A	ENSP00000391417.2	Q4KMQ2-4

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76974 AN: 151784 Hom.: 20484 Cov.: 31

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.507 AC: 77057 AN: 151904 Hom.: 20514 Cov.: 31 AF XY: 0.512 AC XY: 38031 AN XY: 74246

African (AFR) AF: 0.666 AC: 27602 AN: 41436

American (AMR) AF: 0.436 AC: 6660 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1331 AN: 3468

East Asian (EAS) AF: 0.559 AC: 2867 AN: 5126

South Asian (SAS) AF: 0.647 AC: 3108 AN: 4806

European-Finnish (FIN) AF: 0.522 AC: 5502 AN: 10542

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28302 AN: 67940

Other (OTH) AF: 0.486 AC: 1027 AN: 2114

Alfa AF: 0.445 Hom.: 8657

Bravo AF: 0.503

Asia WGS AF: 0.558 AC: 1941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.1
DANN	Benign	0.47
PhyloP100		-0.0090
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: rs965125; hg19: chr12-45722222;