rs2485528

Variant names:

• chr9-101706985-T-C
• rs2485528
• NM_133445.3:c.700-19785A>G

Variant summary

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

The NM_133445.3(GRIN3A):​c.700-19785A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 152,038 control chromosomes in the GnomAD database, including 13,256 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 0.41 (13256 hom., cov: 32)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 4 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 (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN3A	NM_133445.3	c.700-19785A>G		intron_variant	Intron 1 of 8	ENST00000361820.6	NP_597702.2
GRIN3A	XM_011518211.3	c.700-19785A>G		intron_variant	Intron 1 of 6		XP_011516513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN3A	ENST00000361820.6	c.700-19785A>G		intron_variant	Intron 1 of 8	1	NM_133445.3	ENSP00000355155.3

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62500 AN: 151920 Hom.: 13248 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.417

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.411 AC: 62524 AN: 152038 Hom.: 13256 Cov.: 32 AF XY: 0.414 AC XY: 30749 AN XY: 74302

African (AFR) AF: 0.301 AC: 12480 AN: 41472

American (AMR) AF: 0.429 AC: 6558 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1496 AN: 3470

East Asian (EAS) AF: 0.339 AC: 1755 AN: 5170

South Asian (SAS) AF: 0.472 AC: 2268 AN: 4810

European-Finnish (FIN) AF: 0.466 AC: 4923 AN: 10570

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.467 AC: 31713 AN: 67954

Other (OTH) AF: 0.417 AC: 881 AN: 2112

Alfa AF: 0.436 Hom.: 1792

Bravo AF: 0.403

Asia WGS AF: 0.366 AC: 1273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	16
DANN	Benign	0.63
PhyloP100		1.4
Mutation Taster		=100/0	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: rs2485528; hg19: chr9-104469267; COSMIC: COSV62457651;