rs117316516

Variant names:

• chr12-45403426-T-C
• rs117316516
• NM_001025356.3:c.1783-13T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001025356.3(ANO6):​c.1783-13T>C variant causes a intron change. The variant allele was found at a frequency of 0.0229 in 1,605,022 control chromosomes in the GnomAD database, including 695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (43 hom., cov: 32)
  • Exomes 𝑓: 0.024 (652 hom.)
• Consequence: ANO6 NM_001025356.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.61
• Publications: 2 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: Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000293678 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 12-45403426-T-C is Benign according to our data. Variant chr12-45403426-T-C is described in ClinVar as Benign. ClinVar VariationId is 257143.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO6	NM_001025356.3	c.1783-13T>C		intron_variant	Intron 14 of 19	ENST00000320560.13	NP_001020527.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO6	ENST00000320560.13	c.1783-13T>C		intron_variant	Intron 14 of 19	1	NM_001025356.3	ENSP00000320087.8

Frequencies

GnomAD3 genomes AF: 0.0167 AC: 2549 AN: 152250 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.00292

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.0230

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.0251 AC: 6288 AN: 250856 AF XY: 0.0285

Gnomad AFR exome AF: 0.00278

Gnomad AMR exome AF: 0.0104

Gnomad ASJ exome AF: 0.0183

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0255

Gnomad NFE exome AF: 0.0251

Gnomad OTH exome AF: 0.0260

GnomAD4 exome AF: 0.0235 AC: 34161 AN: 1452654 Hom.: 652 Cov.: 30 AF XY: 0.0253 AC XY: 18272 AN XY: 723316

African (AFR) AF: 0.00406 AC: 135 AN: 33260

American (AMR) AF: 0.0105 AC: 469 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0177 AC: 461 AN: 26072

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39626

South Asian (SAS) AF: 0.0698 AC: 6007 AN: 86048

European-Finnish (FIN) AF: 0.0271 AC: 1444 AN: 53352

Middle Eastern (MID) AF: 0.0517 AC: 297 AN: 5750

European-Non Finnish (NFE) AF: 0.0218 AC: 24024 AN: 1103764

Other (OTH) AF: 0.0219 AC: 1315 AN: 60068

GnomAD4 genome AF: 0.0167 AC: 2552 AN: 152368 Hom.: 43 Cov.: 32 AF XY: 0.0173 AC XY: 1290 AN XY: 74518

African (AFR) AF: 0.00293 AC: 122 AN: 41580

American (AMR) AF: 0.0119 AC: 182 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 66 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5196

South Asian (SAS) AF: 0.0731 AC: 353 AN: 4830

European-Finnish (FIN) AF: 0.0230 AC: 244 AN: 10624

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0223 AC: 1515 AN: 68038

Other (OTH) AF: 0.0161 AC: 34 AN: 2114

Alfa AF: 0.0219 Hom.: 48

Bravo AF: 0.0146

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	15
DANN	Benign	0.71
PhyloP100		3.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs117316516; hg19: chr12-45797209;