3-43366927-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018075.5(ANO10):​c.1962C>A​(p.Ser654Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ANO10
NM_018075.5 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.61
Variant links:
Genes affected
ANO10 (HGNC:25519): (anoctamin 10) The transmembrane protein encoded by this gene belongs to the anoctamin family of calcium-activated chloride channels, also known as the transmembrane 16 family. The encoded protein contains eight transmembrane domains with cytosolic N- and C-termini. Defects in this gene may cause autosomal recessive spinocerebellar ataxia-10. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]
SNRK (HGNC:30598): (SNF related kinase) SNRK is a member of the sucrose nonfermenting (SNF)-related kinase family of serine/threonine kinases (Kertesz et al., 2002 [PubMed 12234663]).[supplied by OMIM, Apr 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.033856064).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANO10NM_018075.5 linkc.1962C>A p.Ser654Arg missense_variant Exon 13 of 13 ENST00000292246.8 NP_060545.3 Q9NW15-1A0A024R2S0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANO10ENST00000292246.8 linkc.1962C>A p.Ser654Arg missense_variant Exon 13 of 13 1 NM_018075.5 ENSP00000292246.3 Q9NW15-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152156
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1445578
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
717182
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152156
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ExAC
AF:
0.00000825
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
0.083
DANN
Benign
0.92
DEOGEN2
Benign
0.032
T;.;.;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.010
N
LIST_S2
Benign
0.70
T;T;T;T
M_CAP
Benign
0.0097
T
MetaRNN
Benign
0.034
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;.;.;.
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.67
N;N;N;N
REVEL
Benign
0.26
Sift
Uncertain
0.027
D;D;T;D
Sift4G
Benign
0.45
T;T;T;T
Polyphen
0.0
B;B;B;B
Vest4
0.031
MutPred
0.23
Gain of glycosylation at S654 (P = 0.0167);.;.;.;
MVP
0.11
MPC
0.11
ClinPred
0.065
T
GERP RS
-7.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.041
gMVP
0.20

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: rs756170502; hg19: chr3-43408419; API