4-157312696-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001083619.3(GRIA2):c.487G>T(p.Ala163Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000687 in 1,601,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
GRIA2
NM_001083619.3 missense
NM_001083619.3 missense
Scores
1
3
12
Clinical Significance
Conservation
PhyloP100: 5.43
Genes affected
GRIA2 (HGNC:4572): (glutamate ionotropic receptor AMPA type subunit 2) Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to a family of glutamate receptors that are sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and function as ligand-activated cation channels. These channels are assembled from 4 related subunits, GRIA1-4. The subunit encoded by this gene (GRIA2) is subject to RNA editing (CAG->CGG; Q->R) within the second transmembrane domain, which is thought to render the channel impermeable to Ca(2+). Human and animal studies suggest that pre-mRNA editing is essential for brain function, and defective GRIA2 RNA editing at the Q/R site may be relevant to amyotrophic lateral sclerosis (ALS) etiology. Alternative splicing, resulting in transcript variants encoding different isoforms, (including the flip and flop isoforms that vary in their signal transduction properties), has been noted for this gene. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, GRIA2
BP4
?
Computational evidence support a benign effect (MetaRNN=0.27430806).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIA2 | NM_001083619.3 | c.487G>T | p.Ala163Ser | missense_variant | 4/16 | ENST00000264426.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIA2 | ENST00000264426.14 | c.487G>T | p.Ala163Ser | missense_variant | 4/16 | 1 | NM_001083619.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152058Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
2
AN:
152058
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000821 AC: 2AN: 243490Hom.: 0 AF XY: 0.0000152 AC XY: 2AN XY: 131856
GnomAD3 exomes
AF:
AC:
2
AN:
243490
Hom.:
AF XY:
AC XY:
2
AN XY:
131856
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000621 AC: 9AN: 1449578Hom.: 0 Cov.: 28 AF XY: 0.00000693 AC XY: 5AN XY: 721246
GnomAD4 exome
AF:
AC:
9
AN:
1449578
Hom.:
Cov.:
28
AF XY:
AC XY:
5
AN XY:
721246
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152058Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74282
GnomAD4 genome
?
AF:
AC:
2
AN:
152058
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74282
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
?
AF:
AC:
1
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 | Mar 16, 2022 | The c.487G>T (p.A163S) alteration is located in exon 4 (coding exon 4) of the GRIA2 gene. This alteration results from a G to T substitution at nucleotide position 487, causing the alanine (A) at amino acid position 163 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
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;.;T;T;D;D
Sift4G
Benign
T;T;.;T;T;T;T
Polyphen
0.10, 0.0050
.;.;.;B;B;.;.
Vest4
MutPred
0.42
.;.;Gain of disorder (P = 0.0218);Gain of disorder (P = 0.0218);Gain of disorder (P = 0.0218);.;.;
MVP
MPC
0.65
ClinPred
T
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