Genetic Variant GRIN3A:p.Asp835Asn (chr9-101623429-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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.

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

Publications

26 publications found

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:

ENSG00000299588 (HGNC:):

ENSG00000299588 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GRIN3A	NM_133445.3 link	c.2503G>A	p.Asp835Asn	missense_variant	Exon 5 of 9	ENST00000361820.6	NP_597702.2	Q8TCU5
GRIN3A	XM_011518211.3 link	c.2503G>A	p.Asp835Asn	missense_variant	Exon 5 of 7		XP_011516513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GRIN3A	ENST00000361820.6 link	c.2503G>A	p.Asp835Asn	missense_variant	Exon 5 of 9	1	NM_133445.3	ENSP00000355155.3	Q8TCU5
ENSG00000299588	ENST00000764873.1 link	n.223+17054C>T		intron_variant	Intron 2 of 4
ENSG00000299588	ENST00000764875.1 link	n.198+17054C>T		intron_variant	Intron 2 of 3

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

GnomAD2 exomes

AF:

0.202

AC:

50747

AN:

251234

AF XY:

0.207

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 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

African (AFR)

AF:

0.106

AC:

3488

AN:

33012

American (AMR)

AF:

0.165

AC:

7383

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

6753

AN:

25960

East Asian (EAS)

AF:

0.0477

AC:

1888

AN:

39576

South Asian (SAS)

AF:

0.191

AC:

16381

AN:

85802

European-Finnish (FIN)

AF:

0.248

AC:

13221

AN:

53404

Middle Eastern (MID)

AF:

0.236

AC:

1349

AN:

5726

European-Non Finnish (NFE)

AF:

0.233

AC:

254301

AN:

1090818

Other (OTH)

AF:

0.214

AC:

12762

AN:

59596

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

10188

20375

30563

40750

50938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8212

16424

24636

32848

41060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.194

AC:

29465

AN:

152134

Hom.:

3186

Cov.:

AF XY:

0.192

AC XY:

14291

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.110

AC:

4551

AN:

41526

American (AMR)

AF:

0.198

AC:

3021

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

949

AN:

3472

East Asian (EAS)

AF:

0.0472

AC:

244

AN:

5166

South Asian (SAS)

AF:

0.170

AC:

818

AN:

4822

European-Finnish (FIN)

AF:

0.245

AC:

2593

AN:

10564

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.246

AC:

16705

AN:

67986

Other (OTH)

AF:

0.211

AC:

447

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1199

2398

3596

4795

5994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

312

624

936

1248

1560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.223

Hom.:

13537

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

(source)

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

PhyloP100

7.9

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

Mutation Taster

=84/16

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over