Variant chr11-88508855-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001143831.3(GRM5):c.3376G>T(p.Gly1126Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GRM5
NM_001143831.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37582028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM5	NM_001143831.3 link	c.3376G>T	p.Gly1126Cys	missense_variant	10/10	ENST00000305447.5	NP_001137303.1	P41594-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GRM5	ENST00000305447.5 link	c.3376G>T	p.Gly1126Cys	missense_variant	10/10	1	NM_001143831.3	ENSP00000306138.4	P41594-1
GRM5	ENST00000305432.9 link	c.3280G>T	p.Gly1094Cys	missense_variant	8/8	1		ENSP00000305905.5	P41594-2
GRM5	ENST00000455756.6 link	c.3280G>T	p.Gly1094Cys	missense_variant	9/9	2		ENSP00000405690.2	P41594-2
GRM5-AS1	ENST00000526448.1 link	n.4280C>A		non_coding_transcript_exon_variant	1/6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000555

AC:

AN:

180192

Hom.:

AF XY:

0.00

AC XY:

AN XY:

98876

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000130

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000423

AC:

AN:

1418334

Hom.:

Cov.:

AF XY:

0.00000569

AC XY:

AN XY:

702540

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000550

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.3376G>T (p.G1126C) alteration is located in exon 9 (coding exon 9) of the GRM5 gene. This alteration results from a G to T substitution at nucleotide position 3376, causing the glycine (G) at amino acid position 1126 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.048

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

.;.;T

Eigen

Benign

0.045

Eigen_PC

Benign

0.070

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.82

T;.;T

M_CAP

Pathogenic

0.77

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Benign

-0.30

MutationAssessor

Benign

1.8

.;.;L

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.97

N;N;N

REVEL

Benign

0.25

Sift

Uncertain

0.028

D;D;D

Sift4G

Benign

0.087

T;T;T

Polyphen

0.94

P;P;P

Vest4

0.27

MutPred

0.22

.;.;Loss of helix (P = 0.0237);

MVP

0.54

ClinPred

0.72

GERP RS

4.7

Varity_R

0.28

gMVP

0.49

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