chr11-88508855-C-T

Variant names:

• chr11-88508855-C-T
• rs1274525406
• NM_001143831.3:c.3376G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GRM5 NM_001143831.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.78

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18056339).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM5	NM_001143831.3	c.3376G>A	p.Gly1126Ser	missense_variant	Exon 10 of 10	ENST00000305447.5	NP_001137303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM5	ENST00000305447.5	c.3376G>A	p.Gly1126Ser	missense_variant	Exon 10 of 10	1	NM_001143831.3	ENSP00000306138.4
GRM5	ENST00000305432.9	c.3280G>A	p.Gly1094Ser	missense_variant	Exon 8 of 8	1		ENSP00000305905.5
GRM5	ENST00000455756.6	c.3280G>A	p.Gly1094Ser	missense_variant	Exon 9 of 9	2		ENSP00000405690.2
GRM5-AS1	ENST00000526448.1	n.4280C>T		non_coding_transcript_exon_variant	Exon 1 of 6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1418332 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 702538

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000273

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.16e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.093	.;.;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.87	D;.;D
M_CAP	Pathogenic	0.71	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.8	.;.;L
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.15	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.64	T;T;T
Sift4G	Benign	0.76	T;T;T
Polyphen		0.0070	B;B;B
Vest4		0.070
MutPred		0.15		.;.;Gain of glycosylation at G1126 (P = 0.005);
MVP		0.57
ClinPred		0.31	T
GERP RS		4.7
Varity_R		0.12
gMVP		0.37

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

Other links and lift over

dbSNP: rs1274525406; hg19: chr11-88242023;