Variant rs10989589 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_133445.3(GRIN3A):c.1459G>A(p.Gly487Arg) variant causes a missense change. The variant allele was found at a frequency of 0.384 in 1,613,478 control chromosomes in the GnomAD database, including 122,732 homozygotes. In-silico tool predicts 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 0.33 ( 9337 hom., cov: 32)

Exomes 𝑓: 0.39 ( 113395 hom. )

Consequence

GRIN3A
NM_133445.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.96

Variant links:

Genes affected

GRIN3A (HGNC:16767): (glutamate ionotropic receptor NMDA type subunit 3A) This gene encodes a subunit of the N-methyl-D-aspartate (NMDA) receptors, which belong to the superfamily of glutamate-regulated ion channels, and function in physiological and pathological processes in the central nervous system. This subunit shows greater than 90% identity to the corresponding subunit in rat. Studies in the knockout mouse deficient in this subunit suggest that this gene may be involved in the development of synaptic elements by modulating NMDA receptor activity. [provided by RefSeq, Jul 2008]

GRIN3A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003973037).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN3A	NM_133445.3 linkuse as main transcript	c.1459G>A	p.Gly487Arg	missense_variant	3/9	ENST00000361820.6
GRIN3A	XM_011518211.3 linkuse as main transcript	c.1459G>A	p.Gly487Arg	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN3A	ENST00000361820.6 linkuse as main transcript	c.1459G>A	p.Gly487Arg	missense_variant	3/9	1	NM_133445.3	P1

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50357

AN:

151822

Hom.:

9335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.329

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.434

Gnomad EAS

AF:

0.213

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.375

Gnomad NFE

AF:

0.415

Gnomad OTH

AF:

0.362

GnomAD3 exomes

AF:

0.364

AC:

91429

AN:

251202

Hom.:

17431

AF XY:

0.367

AC XY:

49792

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.160

Gnomad AMR exome

AF:

0.379

Gnomad ASJ exome

AF:

0.422

Gnomad EAS exome

AF:

0.208

Gnomad SAS exome

AF:

0.320

Gnomad FIN exome

AF:

0.391

Gnomad NFE exome

AF:

0.414

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.389

AC:

569110

AN:

1461538

Hom.:

113395

Cov.:

AF XY:

0.389

AC XY:

282490

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.159

Gnomad4 AMR exome

AF:

0.378

Gnomad4 ASJ exome

AF:

0.417

Gnomad4 EAS exome

AF:

0.189

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.388

Gnomad4 NFE exome

AF:

0.409

Gnomad4 OTH exome

AF:

0.380

GnomAD4 genome

AF:

0.332

AC:

50374

AN:

151940

Hom.:

9337

Cov.:

AF XY:

0.329

AC XY:

24421

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.168

Gnomad4 AMR

AF:

0.392

Gnomad4 ASJ

AF:

0.434

Gnomad4 EAS

AF:

0.213

Gnomad4 SAS

AF:

0.302

Gnomad4 FIN

AF:

0.382

Gnomad4 NFE

AF:

0.415

Gnomad4 OTH

AF:

0.362

Alfa

AF:

0.391

Hom.:

18652

Bravo

AF:

0.326

TwinsUK

AF:

0.405

AC:

1502

ALSPAC

AF:

0.397

AC:

1531

ESP6500AA

AF:

0.168

AC:

741

ESP6500EA

AF:

0.413

AC:

3549

ExAC

AF:

0.360

AC:

43655

Asia WGS

AF:

0.303

AC:

1054

AN:

3478

EpiCase

AF:

0.406

EpiControl

AF:

0.407

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0040

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.0000012

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.21

Sift

Benign

0.089

Sift4G

Uncertain

0.043

Polyphen

0.96

Vest4

0.24

MutPred

0.23

Gain of MoRF binding (P = 0.0132);

MPC

0.25

ClinPred

0.039

GERP RS

5.8

Varity_R

0.29

gMVP

0.77

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