rs138817389
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000828.5(GRIA3):c.1181G>A(p.Arg394Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,036,915 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 369 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00090 ( 0 hom., 26 hem., cov: 22)
Exomes 𝑓: 0.0010 ( 0 hom. 343 hem. )
Consequence
GRIA3
NM_000828.5 missense
NM_000828.5 missense
Scores
3
5
6
Clinical Significance
Conservation
PhyloP100: 9.60
Genes affected
GRIA3 (HGNC:4573): (glutamate ionotropic receptor AMPA type subunit 3) 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 at this locus results in different isoforms, which may vary in their signal transduction properties. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0107678175).
BP6
?
Variant X-123403094-G-A is Benign according to our data. Variant chrX-123403094-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 198752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-123403094-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0009 (101/112168) while in subpopulation SAS AF= 0.00259 (7/2700). AF 95% confidence interval is 0.00122. There are 0 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd4 at 26 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIA3 | NM_000828.5 | c.1181G>A | p.Arg394Gln | missense_variant | 8/16 | ENST00000622768.5 | |
GRIA3 | NM_007325.5 | c.1181G>A | p.Arg394Gln | missense_variant | 8/16 | ENST00000620443.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIA3 | ENST00000620443.2 | c.1181G>A | p.Arg394Gln | missense_variant | 8/16 | 1 | NM_007325.5 | P4 | |
GRIA3 | ENST00000622768.5 | c.1181G>A | p.Arg394Gln | missense_variant | 8/16 | 5 | NM_000828.5 | A1 | |
GRIA3 | ENST00000620581.4 | c.1181G>A | p.Arg394Gln | missense_variant, NMD_transcript_variant | 8/17 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000901 AC: 101AN: 112111Hom.: 0 Cov.: 22 AF XY: 0.000757 AC XY: 26AN XY: 34343
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00148 AC: 271AN: 183088Hom.: 1 AF XY: 0.00170 AC XY: 115AN XY: 67650
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GnomAD4 exome AF: 0.00104 AC: 959AN: 924747Hom.: 0 Cov.: 17 AF XY: 0.00137 AC XY: 343AN XY: 251247
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GnomAD4 genome ? AF: 0.000900 AC: 101AN: 112168Hom.: 0 Cov.: 22 AF XY: 0.000756 AC XY: 26AN XY: 34410
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 02, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 06, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Jun 11, 2015 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 02, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Syndromic X-linked intellectual disability 94 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 21, 2019 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
GRIA3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 20, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T;.
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T;T
Polyphen
D;.;D;D
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at