Variant rs10989563 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.2503G>A(p.Asp835Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,590,706 control chromosomes in the GnomAD database, including 40,137 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 0.19 ( 3186 hom., cov: 33)

Exomes 𝑓: 0.22 ( 36951 hom. )

Consequence

GRIN3A
NM_133445.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.91

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=0.001681447).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 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.2503G>A	p.Asp835Asn	missense_variant	5/9	ENST00000361820.6
GRIN3A	XM_011518211.3 linkuse as main transcript	c.2503G>A	p.Asp835Asn	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN3A	ENST00000361820.6 linkuse as main transcript	c.2503G>A	p.Asp835Asn	missense_variant	5/9	1	NM_133445.3	P1

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29458

AN:

152016

Hom.:

3188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.0779

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.0471

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.245

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.210

GnomAD3 exomes

AF:

0.202

AC:

50747

AN:

251234

Hom.:

5742

AF XY:

0.207

AC XY:

28040

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.163

Gnomad ASJ exome

AF:

0.262

Gnomad EAS exome

AF:

0.0405

Gnomad SAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.247

Gnomad NFE exome

AF:

0.241

Gnomad OTH exome

AF:

0.229

GnomAD4 exome

AF:

0.221

AC:

317526

AN:

1438572

Hom.:

36951

Cov.:

AF XY:

0.221

AC XY:

158742

AN XY:

717192

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.165

Gnomad4 ASJ exome

AF:

0.260

Gnomad4 EAS exome

AF:

0.0477

Gnomad4 SAS exome

AF:

0.191

Gnomad4 FIN exome

AF:

0.248

Gnomad4 NFE exome

AF:

0.233

Gnomad4 OTH exome

AF:

0.214

GnomAD4 genome

AF:

0.194

AC:

29465

AN:

152134

Hom.:

3186

Cov.:

AF XY:

0.192

AC XY:

14291

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.198

Gnomad4 ASJ

AF:

0.273

Gnomad4 EAS

AF:

0.0472

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.245

Gnomad4 NFE

AF:

0.246

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.232

Hom.:

9311

Bravo

AF:

0.183

TwinsUK

AF:

0.225

AC:

833

ALSPAC

AF:

0.221

AC:

850

ESP6500AA

AF:

0.0899

AC:

396

ESP6500EA

AF:

0.192

AC:

1649

ExAC

AF:

0.203

AC:

24710

Asia WGS

AF:

0.133

AC:

460

AN:

3478

EpiCase

AF:

0.235

EpiControl

AF:

0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.23

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.6

MutationTaster

Benign

2.9e-8

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.2

REVEL

Benign

0.13

Sift

Benign

0.11

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.19

MPC

0.58

ClinPred

0.0076

GERP RS

5.7

Varity_R

0.18

gMVP

0.76

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