rs17095830

Variant names:

• chr12-45381125-A-G
• rs17095830
• NM_001025356.3:c.1165+3012A>G

Variant summary

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

The NM_001025356.3(ANO6):​c.1165+3012A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 152,220 control chromosomes in the GnomAD database, including 769 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 0.080 (769 hom., cov: 32)
• Consequence: ANO6 NM_001025356.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 23 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 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.1165+3012A>G		intron	N/A	NP_001020527.2	Q4KMQ2-1
	ANO6	NM_001204803.2		c.1228+3012A>G		intron	N/A	NP_001191732.1	Q4KMQ2-2
	ANO6	NM_001142679.2		c.1165+3012A>G		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.1165+3012A>G		intron	N/A	ENSP00000320087.8	Q4KMQ2-1
	ANO6	ENST00000423947.7	TSL:1	c.1228+3012A>G		intron	N/A	ENSP00000409126.3	Q4KMQ2-2
	ANO6	ENST00000425752.6	TSL:1	c.1165+3012A>G		intron	N/A	ENSP00000391417.2	Q4KMQ2-4

Frequencies

GnomAD3 genomes AF: 0.0795 AC: 12088 AN: 152102 Hom.: 763 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0725

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0990

Gnomad FIN AF: 0.0385

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0746

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

GnomAD4 genome AF: 0.0797 AC: 12125 AN: 152220 Hom.: 769 Cov.: 32 AF XY: 0.0812 AC XY: 6046 AN XY: 74430

African (AFR) AF: 0.171 AC: 7097 AN: 41502

American (AMR) AF: 0.0726 AC: 1110 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3470

East Asian (EAS) AF: 0.136 AC: 705 AN: 5186

South Asian (SAS) AF: 0.0999 AC: 482 AN: 4824

European-Finnish (FIN) AF: 0.0385 AC: 409 AN: 10610

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0302 AC: 2055 AN: 68012

Other (OTH) AF: 0.0739 AC: 156 AN: 2112

Alfa AF: 0.0495 Hom.: 865

Bravo AF: 0.0844

Asia WGS AF: 0.118 AC: 409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.0
DANN	Benign	0.57
PhyloP100		-0.018
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: rs17095830; hg19: chr12-45774908;