12-45302107-C-T

Variant summary

Our verdict is Benign. Variant got -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:2
• Conservation: PhyloP100: -0.306

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 257141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-45302107-C-T is described in Lovd as [Benign].
• 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO6	NM_001025356.3	c.150+14C>T		intron_variant		ENST00000320560.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO6	ENST00000320560.13	c.150+14C>T		intron_variant		1	NM_001025356.3	P4

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

GnomAD3 exomes AF: 0.0191 AC: 4785 AN: 251048 Hom.: 71 AF XY: 0.0192 AC XY: 2602 AN XY: 135666

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 SAS exome AF: 0.00539

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

Gnomad4 AFR exome AF: 0.00381

Gnomad4 AMR exome AF: 0.0143

Gnomad4 ASJ exome AF: 0.0106

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.00576

Gnomad4 FIN exome AF: 0.0290

Gnomad4 NFE exome AF: 0.0295

Gnomad4 OTH exome AF: 0.0236

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

Gnomad4 AFR AF: 0.00469

Gnomad4 AMR AF: 0.0177

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.0234

Gnomad4 NFE AF: 0.0308

Gnomad4 OTH AF: 0.0260

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.3
Dann	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs140330230; hg19: chr12-45695890;