rs502434
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000828.5(GRIA3):āc.1200T>Cā(p.Asn400=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.56 ( 12338 hom., 18554 hem., cov: 23)
Exomes š: 0.59 ( 130711 hom. 197798 hem. )
Failed GnomAD Quality Control
Consequence
GRIA3
NM_000828.5 synonymous
NM_000828.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.14
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant X-123403426-T-C is Benign according to our data. Variant chrX-123403426-T-C is described in ClinVar as [Benign]. Clinvar id is 129167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-123403426-T-C is described in Lovd as [Benign]. Variant chrX-123403426-T-C is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.14 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIA3 | NM_000828.5 | c.1200T>C | p.Asn400= | synonymous_variant | 9/16 | ENST00000622768.5 | |
GRIA3 | NM_007325.5 | c.1200T>C | p.Asn400= | synonymous_variant | 9/16 | ENST00000620443.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIA3 | ENST00000620443.2 | c.1200T>C | p.Asn400= | synonymous_variant | 9/16 | 1 | NM_007325.5 | P4 | |
GRIA3 | ENST00000622768.5 | c.1200T>C | p.Asn400= | synonymous_variant | 9/16 | 5 | NM_000828.5 | A1 | |
GRIA3 | ENST00000620581.4 | c.1200T>C | p.Asn400= | synonymous_variant, NMD_transcript_variant | 9/17 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.559 AC: 61905AN: 110644Hom.: 12341 Cov.: 23 AF XY: 0.563 AC XY: 18520AN XY: 32906
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GnomAD3 exomes AF: 0.587 AC: 107501AN: 183055Hom.: 20189 AF XY: 0.587 AC XY: 39666AN XY: 67617
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GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.594 AC: 630466AN: 1061632Hom.: 130711 Cov.: 27 AF XY: 0.585 AC XY: 197798AN XY: 338076
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GnomAD4 genome ? Data not reliable, filtered out with message: InbreedingCoeff AF: 0.559 AC: 61934AN: 110702Hom.: 12338 Cov.: 23 AF XY: 0.563 AC XY: 18554AN XY: 32974
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 26, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:1
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Syndromic X-linked intellectual disability 94 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 2015 | 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. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at