chr11-105612350-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_000829.4(GRIA4):c.163C>T(p.Pro55Ser) 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 benign outcome for this variant. 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
2
7
7
Clinical Significance
Conservation
PhyloP100: 7.57
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, GRIA4
BP4
?
Computational evidence support a benign effect (MetaRNN=0.38955808).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIA4 | NM_000829.4 | c.163C>T | p.Pro55Ser | missense_variant | 3/17 | ENST00000282499.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIA4 | ENST00000282499.10 | c.163C>T | p.Pro55Ser | missense_variant | 3/17 | 5 | NM_000829.4 | A1 |
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: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 03, 2024 | The c.163C>T (p.P55S) alteration is located in exon 3 (coding exon 2) of the GRIA4 gene. This alteration results from a C to T substitution at nucleotide position 163, causing the proline (P) at amino acid position 55 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;N;N;N;N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;T;D;T;T;D;D;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.027, 0.92
.;.;.;B;P;.;.;.;.;P;B
Vest4
0.64, 0.66, 0.69, 0.68, 0.64, 0.66
MutPred
Gain of catalytic residue at P55 (P = 0.0633);Gain of catalytic residue at P55 (P = 0.0633);Gain of catalytic residue at P55 (P = 0.0633);Gain of catalytic residue at P55 (P = 0.0633);Gain of catalytic residue at P55 (P = 0.0633);Gain of catalytic residue at P55 (P = 0.0633);Gain of catalytic residue at P55 (P = 0.0633);Gain of catalytic residue at P55 (P = 0.0633);Gain of catalytic residue at P55 (P = 0.0633);Gain of catalytic residue at P55 (P = 0.0633);Gain of catalytic residue at P55 (P = 0.0633);
MVP
MPC
0.31
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.