rs867126491

Variant names:

• chr7-86786591-C-T
• rs867126491
• NM_000840.3:c.799C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-86786591-C-T
• chr7-86786591-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000840.3(GRM3):​c.799C>T​(p.Pro267Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,378 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GRM3 NM_000840.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.87
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.799C>T	p.Pro267Ser	missense	Exon 3 of 6	NP_000831.2
	GRM3	NM_001363522.2		c.799C>T	p.Pro267Ser	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.799C>T	p.Pro267Ser	missense	Exon 3 of 6	ENSP00000355316.2	Q14832-1
	GRM3	ENST00000439827.1	TSL:1	c.799C>T	p.Pro267Ser	missense	Exon 3 of 5	ENSP00000398767.1	Q14832-2
	GRM3	ENST00000953115.1		c.799C>T	p.Pro267Ser	missense	Exon 3 of 6	ENSP00000623174.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461378 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727018

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.18
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.68	D
Eigen	Benign	0.029
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.030	N
PhyloP100		4.9
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.40
Sift	Benign	0.24	T
Sift4G	Benign	0.27	T
Polyphen		0.020	B
Vest4		0.28
MutPred		0.58		Gain of MoRF binding (P = 0.0394)
MVP		0.69
MPC		1.2
ClinPred		0.81	D
GERP RS		5.2
Varity_R		0.62
gMVP		0.74
Mutation Taster		=45/55	disease causing

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: rs867126491; hg19: chr7-86415907;