rs10989589

Variant names:

• chr9-101670953-C-T
• rs10989589
• NM_133445.3:c.1459G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G487V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.33 (9337 hom., cov: 32)
  • Exomes 𝑓: 0.39 (113395 hom.)
• Consequence: GRIN3A NM_133445.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.96
• Publications: 23 publications found

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]

ENSG00000299588 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133445.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN3A	NM_133445.3	MANE Select	c.1459G>A	p.Gly487Arg	missense	Exon 3 of 9	NP_597702.2	Q8TCU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN3A	ENST00000361820.6	TSL:1 MANE Select	c.1459G>A	p.Gly487Arg	missense	Exon 3 of 9	ENSP00000355155.3	Q8TCU5
	ENSG00000299588	ENST00000764873.1		n.224-53795C>T		intron	N/A
	ENSG00000299588	ENST00000764874.1		n.57+20400C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50357 AN: 151822 Hom.: 9335 Cov.: 32

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

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.: 50 AF XY: 0.389 AC XY: 282490 AN XY: 727096

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

GnomAD4 genome AF: 0.332 AC: 50374 AN: 151940 Hom.: 9337 Cov.: 32 AF XY: 0.329 AC XY: 24421 AN XY: 74258

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.21
Sift	Benign	0.089	T
Sift4G	Uncertain	0.043	D
Polyphen		0.96	P
Vest4		0.24
MutPred		0.23		Gain of MoRF binding (P = 0.0132)
MPC		0.25
ClinPred		0.039	T
GERP RS		5.8
Varity_R		0.29
gMVP		0.77
Mutation Taster		=80/20	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10989589; hg19: chr9-104433235; COSMIC: COSV62453935;