7-126533324-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000845.3(GRM8):c.2058G>A(p.Ala686=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
GRM8
NM_000845.3 synonymous
NM_000845.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.10
Genes affected
GRM8 (HGNC:4600): (glutamate metabotropic receptor 8) 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. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
Variant 7-126533324-C-T is Benign according to our data. Variant chr7-126533324-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 751119.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.1 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GRM8 | NM_000845.3 | c.2058G>A | p.Ala686= | synonymous_variant | 9/11 | ENST00000339582.7 | NP_000836.2 | |
LOC101928357 | XR_927937.3 | n.215-1428C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GRM8 | ENST00000339582.7 | c.2058G>A | p.Ala686= | synonymous_variant | 9/11 | 5 | NM_000845.3 | ENSP00000344173 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000198 AC: 3AN: 151852Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250752Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135504
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461558Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6AN XY: 727058
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GnomAD4 genome AF: 0.0000198 AC: 3AN: 151852Hom.: 0 Cov.: 30 AF XY: 0.0000270 AC XY: 2AN XY: 74120
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 14, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at