rs3744215

chr17-74842510-C-Achr17-74842510-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000835.6(GRIN2C):c.3627G>T(p.Arg1209Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 778,338 control chromosomes in the GnomAD database, including 32,472 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.28 (6313 hom., cov: 33)
  • Exomes 𝑓: 0.28 (26159 hom.)
• Consequence: GRIN2C NM_000835.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.685

Genes affected

GRIN2C (HGNC:4587): (glutamate ionotropic receptor NMDA type subunit 2C) This gene encodes a subunit of the N-methyl-D-aspartate (NMDA) receptor, which is a subtype of ionotropic glutamate receptor. NMDA receptors are found in the central nervous system, are permeable to cations and have an important role in physiological processes such as learning, memory, and synaptic development. The receptor is a tetramer of different subunits (typically heterodimer of subunit 1 with one or more of subunits 2A-D), forming a channel that is permeable to calcium, potassium, and sodium, and whose properties are determined by subunit composition. Alterations in the subunit composition of the receptor are associated with pathophysiological conditions such as Parkinson's disease, Alzheimer's disease, depression, and schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014544725).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN2C	NM_000835.6	c.3627G>T	p.Arg1209Ser	missense_variant	13/13	ENST00000293190.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN2C	ENST00000293190.10	c.3627G>T	p.Arg1209Ser	missense_variant	13/13	1	NM_000835.6	P1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42966 AN: 151956 Hom.: 6302 Cov.: 33

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.288

GnomAD3 exomes AF: 0.280 AC: 68824 AN: 245404 Hom.: 10330 AF XY: 0.283 AC XY: 37854 AN XY: 133678

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.169

Gnomad ASJ exome AF: 0.380

Gnomad EAS exome AF: 0.420

Gnomad SAS exome AF: 0.277

Gnomad FIN exome AF: 0.295

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.280

GnomAD4 exome AF: 0.282 AC: 176421 AN: 626264 Hom.: 26159 Cov.: 0 AF XY: 0.282 AC XY: 96292 AN XY: 341146

Gnomad4 AFR exome AF: 0.298

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.431

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.283 AC: 43004 AN: 152074 Hom.: 6313 Cov.: 33 AF XY: 0.280 AC XY: 20816 AN XY: 74312

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.288

Alfa AF: 0.275 Hom.: 10243

Bravo AF: 0.282

TwinsUK AF: 0.271 AC: 1005

ALSPAC AF: 0.286 AC: 1103

ESP6500AA AF: 0.308 AC: 1356

ESP6500EA AF: 0.283 AC: 2433

ExAC AF: 0.279 AC: 33837

Asia WGS AF: 0.309 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.97	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.023
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.041	D
Polyphen		0.0010	B
Vest4		0.054
MutPred		0.29		Gain of phosphorylation at R1209 (P = 0.0503);
MPC		0.56
ClinPred		0.0087	T
GERP RS		-1.4
Varity_R		0.17
gMVP		0.39

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: rs3744215; hg19: chr17-72838649; COSMIC: COSV53110825; COSMIC: COSV53110825;