rs2228595
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1
The NM_000840.3(GRM3):c.879C>T(p.Ala293=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0624 in 1,612,066 control chromosomes in the GnomAD database, including 3,624 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.051 ( 277 hom., cov: 32)
Exomes 𝑓: 0.064 ( 3347 hom. )
Consequence
GRM3
NM_000840.3 synonymous
NM_000840.3 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.0260
Genes affected
GRM3 (HGNC:4595): (glutamate metabotropic receptor 3) L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. [provided by RefSeq, Jul 2008]
GRM3-AS1 (HGNC:40264): (GRM3 antisense RNA 1)
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP7
?
Synonymous conserved (PhyloP=-0.026 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0964 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRM3 | NM_000840.3 | c.879C>T | p.Ala293= | synonymous_variant | 3/6 | ENST00000361669.7 | |
LOC105375382 | XR_007060408.1 | n.511G>A | non_coding_transcript_exon_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRM3 | ENST00000361669.7 | c.879C>T | p.Ala293= | synonymous_variant | 3/6 | 1 | NM_000840.3 | P1 | |
GRM3 | ENST00000439827.1 | c.879C>T | p.Ala293= | synonymous_variant | 3/5 | 1 | |||
GRM3-AS1 | ENST00000418031.2 | n.982G>A | non_coding_transcript_exon_variant | 3/4 | 3 | ||||
GRM3 | ENST00000454217.1 | c.495C>T | p.Ala165= | synonymous_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0511 AC: 7786AN: 152258Hom.: 277 Cov.: 32
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GnomAD3 exomes AF: 0.0681 AC: 16786AN: 246570Hom.: 698 AF XY: 0.0713 AC XY: 9545AN XY: 133958
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GnomAD4 exome AF: 0.0635 AC: 92745AN: 1459690Hom.: 3347 Cov.: 33 AF XY: 0.0656 AC XY: 47656AN XY: 726266
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GnomAD4 genome ? AF: 0.0511 AC: 7785AN: 152376Hom.: 277 Cov.: 32 AF XY: 0.0524 AC XY: 3905AN XY: 74508
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ClinVar
Not reported inComputational scores
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Name
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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