Variant rs3744215 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 13/20 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.685

Variant links:

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]

GRIN2C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
GRIN2C	NM_000835.6 linkuse as main transcript	c.3627G>T	p.Arg1209Ser	missense_variant	13/13	ENST00000293190.10	NP_000826.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2C	ENST00000293190.10 linkuse as main transcript	c.3627G>T	p.Arg1209Ser	missense_variant	13/13	1	NM_000835.6	ENSP00000293190	P1

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

42966

AN:

151956

Hom.:

6302

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.282

AC XY:

96292

AN XY:

341146

show subpopulations

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.:

AF XY:

0.280

AC XY:

20816

AN XY:

74312

show subpopulations

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

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.97

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.58

REVEL

Benign

0.023

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.041

Polyphen

0.0010

Vest4

0.054

MutPred

0.29

Gain of phosphorylation at R1209 (P = 0.0503);

MPC

0.56

ClinPred

0.0087

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over