NM_000840.3:c.887C>G

Variant names:

• chr7-86786679-C-G
• rs1200874782
• NM_000840.3:c.887C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000840.3(GRM3):​c.887C>G​(p.Thr296Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GRM3 NM_000840.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41352713).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000840.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM3	NM_000840.3	MANE Select	c.887C>G	p.Thr296Ser	missense	Exon 3 of 6	NP_000831.2
	GRM3	NM_001363522.2		c.887C>G	p.Thr296Ser	missense	Exon 3 of 5	NP_001350451.1	Q14832-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM3	ENST00000361669.7	TSL:1 MANE Select	c.887C>G	p.Thr296Ser	missense	Exon 3 of 6	ENSP00000355316.2	Q14832-1
	GRM3	ENST00000439827.1	TSL:1	c.887C>G	p.Thr296Ser	missense	Exon 3 of 5	ENSP00000398767.1	Q14832-2
	GRM3	ENST00000953115.1		c.887C>G	p.Thr296Ser	missense	Exon 3 of 6	ENSP00000623174.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.075
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.5
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.33
Sift	Benign	0.39	T
Sift4G	Benign	0.44	T
Polyphen		0.0040	B
Vest4		0.49
MutPred		0.53		Gain of disorder (P = 0.0615)
MVP		0.61
MPC		1.0
ClinPred		0.38	T
GERP RS		6.1
Varity_R		0.56
gMVP		0.52
Mutation Taster		=67/33	polymorphism

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

Other links and lift over

dbSNP: rs1200874782; hg19: chr7-86415995;