rs7299561

Variant names:

• chr12-45302045-C-T
• rs7299561
• NM_001025356.3:c.102C>T
• ANO6 p.Pro34Pro

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001025356.3(ANO6):​c.102C>T​(p.Pro34Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00862 in 1,613,810 control chromosomes in the GnomAD database, including 927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (479 hom., cov: 33)
  • Exomes 𝑓: 0.0049 (448 hom.)
• Consequence: ANO6 NM_001025356.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.338
• Publications: 5 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000293678 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 12-45302045-C-T is Benign according to our data. Variant chr12-45302045-C-T is described in ClinVar as Benign. ClinVar VariationId is 257139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.338 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 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.102C>T	p.Pro34Pro	synonymous	Exon 2 of 20	NP_001020527.2	Q4KMQ2-1
	ANO6	NM_001204803.2		c.165C>T	p.Pro55Pro	synonymous	Exon 3 of 21	NP_001191732.1	Q4KMQ2-2
	ANO6	NM_001142679.2		c.102C>T	p.Pro34Pro	synonymous	Exon 2 of 20	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.102C>T	p.Pro34Pro	synonymous	Exon 2 of 20	ENSP00000320087.8	Q4KMQ2-1
	ANO6	ENST00000423947.7	TSL:1	c.165C>T	p.Pro55Pro	synonymous	Exon 3 of 21	ENSP00000409126.3	Q4KMQ2-2
	ANO6	ENST00000425752.6	TSL:1	c.102C>T	p.Pro34Pro	synonymous	Exon 2 of 20	ENSP00000391417.2	Q4KMQ2-4

Frequencies

GnomAD3 genomes AF: 0.0439 AC: 6677 AN: 152022 Hom.: 479 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0260

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0354

GnomAD2 exomes AF: 0.0121 AC: 3037 AN: 251294 AF XY: 0.00826

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.00869

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000818

Gnomad OTH exome AF: 0.00620

GnomAD4 exome AF: 0.00493 AC: 7211 AN: 1461670 Hom.: 448 Cov.: 32 AF XY: 0.00422 AC XY: 3065 AN XY: 727140

African (AFR) AF: 0.159 AC: 5312 AN: 33466

American (AMR) AF: 0.00984 AC: 440 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00122 AC: 32 AN: 26124

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39690

South Asian (SAS) AF: 0.000939 AC: 81 AN: 86258

European-Finnish (FIN) AF: 0.000262 AC: 14 AN: 53416

Middle Eastern (MID) AF: 0.0109 AC: 63 AN: 5766

European-Non Finnish (NFE) AF: 0.000522 AC: 580 AN: 1111864

Other (OTH) AF: 0.0114 AC: 688 AN: 60380

GnomAD4 genome AF: 0.0440 AC: 6699 AN: 152140 Hom.: 479 Cov.: 33 AF XY: 0.0422 AC XY: 3141 AN XY: 74392

African (AFR) AF: 0.149 AC: 6163 AN: 41460

American (AMR) AF: 0.0259 AC: 396 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10594

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68022

Other (OTH) AF: 0.0350 AC: 74 AN: 2114

Alfa AF: 0.0205 Hom.: 140

Bravo AF: 0.0516

Asia WGS AF: 0.00982 AC: 34 AN: 3478

EpiCase AF: 0.00131

EpiControl AF: 0.000889

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.1
DANN	Benign	0.48
PhyloP100		-0.34
Mutation Taster		=97/3	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7299561;

hg19: chr12-45695828;