12-45357362-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001025356.3(ANO6):​c.936C>T​(p.Ala312Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,956 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 13 hom., cov: 32)
Exomes 𝑓: 0.010 ( 93 hom. )

Consequence

ANO6
NM_001025356.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.597
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 12-45357362-C-T is Benign according to our data. Variant chr12-45357362-C-T is described in ClinVar as [Benign]. Clinvar id is 257148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.597 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00774 (1178/152286) while in subpopulation NFE AF= 0.0133 (903/68022). AF 95% confidence interval is 0.0126. There are 13 homozygotes in gnomad4. There are 524 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANO6NM_001025356.3 linkc.936C>T p.Ala312Ala synonymous_variant Exon 8 of 20 ENST00000320560.13 NP_001020527.2 Q4KMQ2-1B3KX12

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANO6ENST00000320560.13 linkc.936C>T p.Ala312Ala synonymous_variant Exon 8 of 20 1 NM_001025356.3 ENSP00000320087.8 Q4KMQ2-1

Frequencies

GnomAD3 genomes
AF:
0.00775
AC:
1179
AN:
152168
Hom.:
13
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00181
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00616
Gnomad ASJ
AF:
0.00663
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00394
Gnomad FIN
AF:
0.00433
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0133
Gnomad OTH
AF:
0.00861
GnomAD3 exomes
AF:
0.00798
AC:
2006
AN:
251398
Hom.:
10
AF XY:
0.00836
AC XY:
1136
AN XY:
135868
show subpopulations
Gnomad AFR exome
AF:
0.00166
Gnomad AMR exome
AF:
0.00321
Gnomad ASJ exome
AF:
0.00476
Gnomad EAS exome
AF:
0.000218
Gnomad SAS exome
AF:
0.00418
Gnomad FIN exome
AF:
0.00642
Gnomad NFE exome
AF:
0.0132
Gnomad OTH exome
AF:
0.00832
GnomAD4 exome
AF:
0.0104
AC:
15217
AN:
1461670
Hom.:
93
Cov.:
31
AF XY:
0.0103
AC XY:
7457
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.00119
Gnomad4 AMR exome
AF:
0.00313
Gnomad4 ASJ exome
AF:
0.00494
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.00464
Gnomad4 FIN exome
AF:
0.00766
Gnomad4 NFE exome
AF:
0.0121
Gnomad4 OTH exome
AF:
0.0102
GnomAD4 genome
AF:
0.00774
AC:
1178
AN:
152286
Hom.:
13
Cov.:
32
AF XY:
0.00704
AC XY:
524
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.00180
Gnomad4 AMR
AF:
0.00615
Gnomad4 ASJ
AF:
0.00663
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00373
Gnomad4 FIN
AF:
0.00433
Gnomad4 NFE
AF:
0.0133
Gnomad4 OTH
AF:
0.00852
Alfa
AF:
0.0104
Hom.:
6
Bravo
AF:
0.00730
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.0109
EpiControl
AF:
0.0119

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Sep 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

ANO6: BP4, BP7, BS1, BS2 -

Jan 29, 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
-0.44
CADD
Benign
0.052
DANN
Benign
0.54
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs145896287; hg19: chr12-45751145; COSMIC: COSV57662254; API