Variant 7-86838938-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000840.3(GRM3):c.1424G>A(p.Gly475Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,613,628 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0092 ( 12 hom., cov: 32)

Exomes 𝑓: 0.012 ( 125 hom. )

Consequence

GRM3
NM_000840.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.46

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007987589).

BP6

Variant 7-86838938-G-A is Benign according to our data. Variant chr7-86838938-G-A is described in ClinVar as [Benign]. Clinvar id is 2657657.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1397 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM3	NM_000840.3 link	c.1424G>A	p.Gly475Asp	missense_variant	4/6	ENST00000361669.7	NP_000831.2	Q14832-1A4D1D0
GRM3	XM_047420268.1 link	c.1424G>A	p.Gly475Asp	missense_variant	5/7		XP_047276224.1
GRM3	NM_001363522.2 link	c.1325-11432G>A		intron_variant			NP_001350451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM3	ENST00000361669.7 link	c.1424G>A	p.Gly475Asp	missense_variant	4/6	1	NM_000840.3	ENSP00000355316.2		Q14832-1
GRM3	ENST00000439827.1 link	c.1325-11432G>A		intron_variant		1		ENSP00000398767.1		Q14832-2

Frequencies

GnomAD3 genomes

AF:

0.00919

AC:

1398

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00933

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0130

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.0102

AC:

2559

AN:

251210

Hom.:

AF XY:

0.0108

AC XY:

1461

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00885

Gnomad ASJ exome

AF:

0.0172

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0114

Gnomad FIN exome

AF:

0.00356

Gnomad NFE exome

AF:

0.0135

Gnomad OTH exome

AF:

0.0137

GnomAD4 exome

AF:

0.0120

AC:

17552

AN:

1461310

Hom.:

125

Cov.:

AF XY:

0.0119

AC XY:

8681

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.00977

Gnomad4 ASJ exome

AF:

0.0165

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0111

Gnomad4 FIN exome

AF:

0.00361

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.0130

GnomAD4 genome

AF:

0.00917

AC:

1397

AN:

152318

Hom.:

Cov.:

AF XY:

0.00881

AC XY:

656

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.0143

Gnomad4 ASJ

AF:

0.0190

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00934

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.0130

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.0121

Hom.:

Bravo

AF:

0.0102

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.0169

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.0137

AC:

118

ExAC

AF:

0.0106

AC:

1286

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0157

EpiControl

AF:

0.0157

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 submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

GRM3: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.20

Eigen

Benign

-0.14

Eigen_PC

Benign

0.097

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0080

MetaSVM

Benign

-0.47

MutationAssessor

Benign

0.95

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.44

REVEL

Uncertain

0.32

Sift

Benign

0.31

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.073

MPC

0.53

ClinPred

0.0085

GERP RS

5.9

Varity_R

0.33

gMVP

0.54

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over