rs117316516

chr12-45403426-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001025356.3(ANO6):c.1783-13T>C variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.61

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]

LOC105369743 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
ANO6	NM_001025356.3	c.1783-13T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000320560.13
LOC105369743	XR_944886.3	n.1353-5202A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO6	ENST00000320560.13	c.1783-13T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001025356.3	P4

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

GnomAD3 exomes AF: 0.0251 AC: 6288 AN: 250856 Hom.: 154 AF XY: 0.0285 AC XY: 3870 AN XY: 135626

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 SAS exome AF: 0.0701

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

Gnomad4 AFR exome AF: 0.00406

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.0177

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0698

Gnomad4 FIN exome AF: 0.0271

Gnomad4 NFE exome AF: 0.0218

Gnomad4 OTH exome AF: 0.0219

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

Gnomad4 AFR AF: 0.00293

Gnomad4 AMR AF: 0.0119

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0731

Gnomad4 FIN AF: 0.0230

Gnomad4 NFE AF: 0.0223

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0187 Hom.: 8

Bravo AF: 0.0146

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	15
Dann	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs117316516; hg19: chr12-45797209;