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GeneBe

7-86839542-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_000840.3(GRM3):c.2028C>T(p.Gly676=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000426 in 1,607,258 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

GRM3
NM_000840.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.260
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-86839542-C-T is Benign according to our data. Variant chr7-86839542-C-T is described in ClinVar as [Benign]. Clinvar id is 709868.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.26 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 352 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRM3NM_000840.3 linkuse as main transcriptc.2028C>T p.Gly676= synonymous_variant 4/6 ENST00000361669.7
GRM3XM_047420268.1 linkuse as main transcriptc.2028C>T p.Gly676= synonymous_variant 5/7
GRM3NM_001363522.2 linkuse as main transcriptc.1325-10828C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRM3ENST00000361669.7 linkuse as main transcriptc.2028C>T p.Gly676= synonymous_variant 4/61 NM_000840.3 P1Q14832-1
GRM3ENST00000439827.1 linkuse as main transcriptc.1325-10828C>T intron_variant 1 Q14832-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00231
AC:
352
AN:
152100
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00746
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00236
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000598
AC:
147
AN:
245736
Hom.:
0
AF XY:
0.000482
AC XY:
64
AN XY:
132670
show subpopulations
Gnomad AFR exome
AF:
0.00740
Gnomad AMR exome
AF:
0.000586
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.0000680
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000180
Gnomad OTH exome
AF:
0.000336
GnomAD4 exome
AF:
0.000228
AC:
332
AN:
1455040
Hom.:
1
Cov.:
33
AF XY:
0.000210
AC XY:
152
AN XY:
723154
show subpopulations
Gnomad4 AFR exome
AF:
0.00659
Gnomad4 AMR exome
AF:
0.000768
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000704
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000271
Gnomad4 OTH exome
AF:
0.000600
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00231
AC:
352
AN:
152218
Hom.:
0
Cov.:
32
AF XY:
0.00231
AC XY:
172
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.00744
Gnomad4 AMR
AF:
0.00236
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00200
Hom.:
0
Bravo
AF:
0.00295
Asia WGS
AF:
0.00433
AC:
15
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.34
Cadd
Benign
9.5
Dann
Benign
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs112184476; hg19: chr7-86468858; COSMIC: COSV64470286; API