chr11-105612353-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP2
The NM_000829.4(GRIA4):c.166A>C(p.Asn56His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
GRIA4
NM_000829.4 missense
NM_000829.4 missense
Scores
3
5
8
Clinical Significance
Conservation
PhyloP100: 8.95
Genes affected
GRIA4 (HGNC:4574): (glutamate ionotropic receptor AMPA type subunit 4) Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes composed of multiple subunits, arranged to form ligand-gated ion channels. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. The subunit encoded by this gene belongs to a family of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)-sensitive glutamate receptors, and is subject to RNA editing (AGA->GGA; R->G). Alternative splicing of this gene results in transcript variants encoding different isoforms, which may vary in their signal transduction properties. Some haplotypes of this gene show a positive association with schizophrenia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM1
?
In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity GRIA4_HUMAN
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, GRIA4
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIA4 | NM_000829.4 | c.166A>C | p.Asn56His | missense_variant | 3/17 | ENST00000282499.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIA4 | ENST00000282499.10 | c.166A>C | p.Asn56His | missense_variant | 3/17 | 5 | NM_000829.4 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;D;D;D;D;D
Sift4G
Benign
T;T;T;D;D;T;T;T;D;D;D
Polyphen
1.0, 1.0
.;.;.;D;D;.;.;.;.;D;D
Vest4
0.69, 0.69, 0.79, 0.70, 0.71, 0.71
MutPred
Gain of catalytic residue at N56 (P = 0.0332);Gain of catalytic residue at N56 (P = 0.0332);Gain of catalytic residue at N56 (P = 0.0332);Gain of catalytic residue at N56 (P = 0.0332);Gain of catalytic residue at N56 (P = 0.0332);Gain of catalytic residue at N56 (P = 0.0332);Gain of catalytic residue at N56 (P = 0.0332);Gain of catalytic residue at N56 (P = 0.0332);Gain of catalytic residue at N56 (P = 0.0332);Gain of catalytic residue at N56 (P = 0.0332);Gain of catalytic residue at N56 (P = 0.0332);
MVP
MPC
0.92
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.