chr12-101096604-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_ModeratePP5_Moderate
The NM_001286615.2(ANO4):c.1807A>G(p.Asn603Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
ANO4
NM_001286615.2 missense
NM_001286615.2 missense
Scores
7
5
1
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, ANO4
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.868
PP5
?
Variant 12-101096604-A-G is Pathogenic according to our data. Variant chr12-101096604-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 3067134.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANO4 | NM_001286615.2 | c.1807A>G | p.Asn603Asp | missense_variant | 19/28 | ENST00000392977.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANO4 | ENST00000392977.8 | c.1807A>G | p.Asn603Asp | missense_variant | 19/28 | 2 | NM_001286615.2 | ||
ANO4 | ENST00000644049.1 | c.2305A>G | p.Asn769Asp | missense_variant | 21/30 | ||||
ANO4 | ENST00000392979.7 | c.1702A>G | p.Asn568Asp | missense_variant | 18/27 | 2 | P1 | ||
ANO4 | ENST00000550015.1 | n.461A>G | non_coding_transcript_exon_variant | 6/15 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Pathogenic:1
Pathogenic, criteria provided, single submitter | in vitro;research | Institute of Medical Genetics, University of Zurich | Mar 26, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
Polyphen
1.0
.;D;D
Vest4
0.94, 0.95
MutPred
0.67
.;.;Loss of catalytic residue at N603 (P = 0.0954);
MVP
0.26
MPC
1.4
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.