12-45302107-C-T

Variant names:

• chr12-45302107-C-T
• rs140330230
• NM_001025356.3:c.150+14C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001025356.3(ANO6):​c.150+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 1,610,344 control chromosomes in the GnomAD database, including 641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (42 hom., cov: 33)
  • Exomes 𝑓: 0.026 (599 hom.)
• Consequence: ANO6 NM_001025356.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.306
• 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=-0.84).
• BP6: Variant 12-45302107-C-T is Benign according to our data. Variant chr12-45302107-C-T is described in ClinVar as Benign. ClinVar VariationId is 257141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0197 (2995/152274) while in subpopulation NFE AF = 0.0308 (2097/68010). AF 95% confidence interval is 0.0297. There are 42 homozygotes in GnomAd4. There are 1435 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO6	NM_001025356.3	c.150+14C>T		intron_variant	Intron 2 of 19	ENST00000320560.13	NP_001020527.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO6	ENST00000320560.13	c.150+14C>T		intron_variant	Intron 2 of 19	1	NM_001025356.3	ENSP00000320087.8

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2995 AN: 152158 Hom.: 42 Cov.: 33

Gnomad AFR AF: 0.00471

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0178

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.0234

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0308

Gnomad OTH AF: 0.0263

GnomAD2 exomes AF: 0.0191 AC: 4785 AN: 251048 AF XY: 0.0192

Gnomad AFR exome AF: 0.00412

Gnomad AMR exome AF: 0.0135

Gnomad ASJ exome AF: 0.00953

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0277

Gnomad NFE exome AF: 0.0286

Gnomad OTH exome AF: 0.0237

GnomAD4 exome AF: 0.0256 AC: 37382 AN: 1458070 Hom.: 599 Cov.: 30 AF XY: 0.0251 AC XY: 18217 AN XY: 725624

African (AFR) AF: 0.00381 AC: 127 AN: 33356

American (AMR) AF: 0.0143 AC: 639 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0106 AC: 277 AN: 26090

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39666

South Asian (SAS) AF: 0.00576 AC: 496 AN: 86172

European-Finnish (FIN) AF: 0.0290 AC: 1551 AN: 53394

Middle Eastern (MID) AF: 0.0193 AC: 111 AN: 5754

European-Non Finnish (NFE) AF: 0.0295 AC: 32751 AN: 1108690

Other (OTH) AF: 0.0236 AC: 1423 AN: 60256

GnomAD4 genome AF: 0.0197 AC: 2995 AN: 152274 Hom.: 42 Cov.: 33 AF XY: 0.0193 AC XY: 1435 AN XY: 74444

African (AFR) AF: 0.00469 AC: 195 AN: 41566

American (AMR) AF: 0.0177 AC: 271 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4826

European-Finnish (FIN) AF: 0.0234 AC: 248 AN: 10602

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0308 AC: 2097 AN: 68010

Other (OTH) AF: 0.0260 AC: 55 AN: 2116

Alfa AF: 0.0230 Hom.: 5

Bravo AF: 0.0183

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

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

- -

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	-0.84
CADD	Benign	1.3
DANN	Benign	0.72
PhyloP100		-0.31
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: rs140330230; hg19: chr12-45695890;