Genetic Variant GRM5:p.Gly1126Ser (chr11-88508855-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001143831.3(GRM5):c.3376G>A(p.Gly1126Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,418,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1126C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GRM5
NM_001143831.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78

Publications

0 publications found

Variant links:

Genes affected

GRM5 (HGNC:4597): (glutamate metabotropic receptor 5) This gene encodes a member of the G-protein coupled receptor 3 protein family. The encoded protein is a metabatropic glutamate receptor, whose signaling activates a phosphatidylinositol-calcium second messenger system. This protein may be involved in the regulation of neural network activity and synaptic plasticity. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. A pseudogene of this gene has been defined on chromosome 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

GRM5 links:

GRM5-AS1 (HGNC:40265): (GRM5 antisense RNA 1)

GRM5-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18056339).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143831.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRM5	NM_001143831.3	MANE Select	c.3376G>A	p.Gly1126Ser	missense	Exon 10 of 10	NP_001137303.1	P41594-1
GRM5	NM_000842.5		c.3280G>A	p.Gly1094Ser	missense	Exon 9 of 9	NP_000833.1	P41594-2
GRM5	NM_001384268.1		c.3280G>A	p.Gly1094Ser	missense	Exon 9 of 9	NP_001371197.1	P41594-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRM5	ENST00000305447.5	TSL:1 MANE Select	c.3376G>A	p.Gly1126Ser	missense	Exon 10 of 10	ENSP00000306138.4	P41594-1
GRM5	ENST00000305432.9	TSL:1	c.3280G>A	p.Gly1094Ser	missense	Exon 8 of 8	ENSP00000305905.5	P41594-2
GRM5	ENST00000962224.1		c.3376G>A	p.Gly1126Ser	missense	Exon 10 of 10	ENSP00000632283.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

180192

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1418332

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

702538

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30960

American (AMR)

AF:

0.00

AC:

AN:

38596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25084

East Asian (EAS)

AF:

0.0000273

AC:

AN:

36570

South Asian (SAS)

AF:

0.00

AC:

AN:

80590

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

9.16e-7

AC:

AN:

1091694

Other (OTH)

AF:

0.00

AC:

AN:

58720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.093

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.71

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.8

PhyloP100

3.8

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.15

REVEL

Benign

0.20

Sift

Benign

0.64

Sift4G

Benign

0.76

Polyphen

0.0070

Vest4

0.070

MutPred

0.15

Gain of glycosylation at G1126 (P = 0.005)

MVP

0.57

ClinPred

0.31

GERP RS

4.7

Varity_R

0.12

gMVP

0.37

Mutation Taster

=72/28

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over