rs1019146684
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_000828.5(GRIA3):c.585C>T(p.Asn195=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000457 in 1,093,706 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 22)
Exomes 𝑓: 0.0000046 ( 0 hom. 2 hem. )
Consequence
GRIA3
NM_000828.5 synonymous
NM_000828.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.968
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
Variant X-123326102-C-T is Benign according to our data. Variant chrX-123326102-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 435360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.968 with no splicing effect.
BS2
?
High Hemizygotes in GnomAdExome4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIA3 | NM_000828.5 | c.585C>T | p.Asn195= | synonymous_variant | 4/16 | ENST00000622768.5 | |
GRIA3 | NM_007325.5 | c.585C>T | p.Asn195= | synonymous_variant | 4/16 | ENST00000620443.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIA3 | ENST00000620443.2 | c.585C>T | p.Asn195= | synonymous_variant | 4/16 | 1 | NM_007325.5 | P4 | |
GRIA3 | ENST00000622768.5 | c.585C>T | p.Asn195= | synonymous_variant | 4/16 | 5 | NM_000828.5 | A1 | |
GRIA3 | ENST00000620581.4 | c.585C>T | p.Asn195= | synonymous_variant, NMD_transcript_variant | 4/17 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00000545 AC: 1AN: 183361Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67847
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GnomAD4 exome AF: 0.00000457 AC: 5AN: 1093706Hom.: 0 Cov.: 29 AF XY: 0.00000557 AC XY: 2AN XY: 359180
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GnomAD4 genome ? Cov.: 22
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 25, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 19, 2022 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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