rs770877324

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001025356.3(ANO6):​c.143C>G​(p.Pro48Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P48L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

ANO6
NM_001025356.3 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.45
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28719413).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANO6NM_001025356.3 linkc.143C>G p.Pro48Arg missense_variant Exon 2 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.143C>G p.Pro48Arg missense_variant Exon 2 of 20 1 NM_001025356.3 ENSP00000320087.8 Q4KMQ2-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251252
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135780
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461496
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727060
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.63
BayesDel_addAF
Benign
0.0084
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.083
.;.;T;.
Eigen
Benign
-0.0026
Eigen_PC
Benign
0.056
FATHMM_MKL
Benign
0.60
D
LIST_S2
Uncertain
0.86
D;D;D;D
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.29
T;T;T;T
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Benign
0.81
L;.;L;.
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.3
N;N;N;N
REVEL
Benign
0.13
Sift
Uncertain
0.029
D;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;D
Polyphen
0.29
.;.;B;.
Vest4
0.47
MutPred
0.23
Gain of helix (P = 0.0082);.;Gain of helix (P = 0.0082);.;
MVP
0.45
MPC
0.20
ClinPred
0.70
D
GERP RS
4.8
Varity_R
0.10
gMVP
0.39

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: rs770877324; hg19: chr12-45695869; API