Variant chr7-86786671-C-T details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0260

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]

GRM3 links:

GRM3-AS1 (HGNC:40264): (GRM3 antisense RNA 1)

GRM3-AS1 links:

LOC105375382 (HGNC:):

LOC105375382 links:

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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 linkuse as main transcript	c.879C>T	p.Ala293=	synonymous_variant	3/6	ENST00000361669.7
LOC105375382	XR_007060408.1 linkuse as main transcript	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 linkuse as main transcript	c.879C>T	p.Ala293=	synonymous_variant	3/6	1	NM_000840.3	P1	Q14832-1
GRM3	ENST00000439827.1 linkuse as main transcript	c.879C>T	p.Ala293=	synonymous_variant	3/5	1			Q14832-2
GRM3-AS1	ENST00000418031.2 linkuse as main transcript	n.982G>A		non_coding_transcript_exon_variant	3/4	3
GRM3	ENST00000454217.1 linkuse as main transcript	c.495C>T	p.Ala165=	synonymous_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0511

AC:

7786

AN:

152258

Hom.:

277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0709

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.0620

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.0459

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0619

Gnomad OTH

AF:

0.0635

GnomAD3 exomes

AF:

0.0681

AC:

16786

AN:

246570

Hom.:

698

AF XY:

0.0713

AC XY:

9545

AN XY:

133958

show subpopulations

Gnomad AFR exome

AF:

0.00951

Gnomad AMR exome

AF:

0.0761

Gnomad ASJ exome

AF:

0.146

Gnomad EAS exome

AF:

0.0671

Gnomad SAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.0486

Gnomad NFE exome

AF:

0.0596

Gnomad OTH exome

AF:

0.0760

GnomAD4 exome

AF:

0.0635

AC:

92745

AN:

1459690

Hom.:

3347

Cov.:

AF XY:

0.0656

AC XY:

47656

AN XY:

726266

show subpopulations

Gnomad4 AFR exome

AF:

0.00965

Gnomad4 AMR exome

AF:

0.0750

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.0564

Gnomad4 SAS exome

AF:

0.106

Gnomad4 FIN exome

AF:

0.0476

Gnomad4 NFE exome

AF:

0.0597

Gnomad4 OTH exome

AF:

0.0721

GnomAD4 genome

AF:

0.0511

AC:

7785

AN:

152376

Hom.:

277

Cov.:

AF XY:

0.0524

AC XY:

3905

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0119

Gnomad4 AMR

AF:

0.0709

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.0618

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.0459

Gnomad4 NFE

AF:

0.0619

Gnomad4 OTH

AF:

0.0638

Alfa

AF:

0.0633

Hom.:

393

Bravo

AF:

0.0502

Asia WGS

AF:

0.0610

AC:

213

AN:

3478

EpiCase

AF:

0.0672

EpiControl

AF:

0.0673

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.91

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over