dbSNP rs10989589: GRIN3A:p.Gly487Arg (chr9-101670953-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.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.

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

Publications

23 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=0.003973037).

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 rank	MANE	Protein	UniProt
GRIN3A	NM_133445.3 link	c.1459G>A	p.Gly487Arg	missense_variant	Exon 3 of 9	ENST00000361820.6	NP_597702.2	Q8TCU5
GRIN3A	XM_011518211.3 link	c.1459G>A	p.Gly487Arg	missense_variant	Exon 3 of 7		XP_011516513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN3A	ENST00000361820.6 link	c.1459G>A	p.Gly487Arg	missense_variant	Exon 3 of 9	1	NM_133445.3	ENSP00000355155.3		Q8TCU5

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

GnomAD2 exomes

AF:

0.364

AC:

91429

AN:

251202

AF XY:

0.367

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 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

African (AFR)

AF:

0.159

AC:

5328

AN:

33464

American (AMR)

AF:

0.378

AC:

16878

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.417

AC:

10892

AN:

26130

East Asian (EAS)

AF:

0.189

AC:

7496

AN:

39696

South Asian (SAS)

AF:

0.318

AC:

27429

AN:

86238

European-Finnish (FIN)

AF:

0.388

AC:

20709

AN:

53418

Middle Eastern (MID)

AF:

0.392

AC:

2257

AN:

5762

European-Non Finnish (NFE)

AF:

0.409

AC:

455159

AN:

1111738

Other (OTH)

AF:

0.380

AC:

22962

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

20803

41605

62408

83210

104013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13718

27436

41154

54872

68590

<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:

0.332

AC:

50374

AN:

151940

Hom.:

9337

Cov.:

AF XY:

0.329

AC XY:

24421

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.168

AC:

6952

AN:

41484

American (AMR)

AF:

0.392

AC:

5988

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.434

AC:

1508

AN:

3472

East Asian (EAS)

AF:

0.213

AC:

1094

AN:

5134

South Asian (SAS)

AF:

0.302

AC:

1451

AN:

4806

European-Finnish (FIN)

AF:

0.382

AC:

4045

AN:

10580

Middle Eastern (MID)

AF:

0.359

AC:

104

AN:

290

European-Non Finnish (NFE)

AF:

0.415

AC:

28169

AN:

67900

Other (OTH)

AF:

0.362

AC:

764

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1620

3241

4861

6482

8102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.380

Hom.:

24478

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

(source)

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

PhyloP100

5.0

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

Mutation Taster

=80/20

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

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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