rs2485523

Variant names:

• chr9-101694954-T-C
• rs2485523
• NM_133445.3:c.700-7754A>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.700-7754A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,108 control chromosomes in the GnomAD database, including 46,826 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 0.78 (46826 hom., cov: 32)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN3A	NM_133445.3	c.700-7754A>G		intron_variant	Intron 1 of 8	ENST00000361820.6	NP_597702.2
GRIN3A	XM_011518211.3	c.700-7754A>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.700-7754A>G		intron_variant	Intron 1 of 8	1	NM_133445.3	ENSP00000355155.3

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118739 AN: 151988 Hom.: 46776 Cov.: 32

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.850

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.770

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

GnomAD4 genome AF: 0.781 AC: 118853 AN: 152108 Hom.: 46826 Cov.: 32 AF XY: 0.781 AC XY: 58047 AN XY: 74350

African (AFR) AF: 0.837 AC: 34737 AN: 41522

American (AMR) AF: 0.741 AC: 11307 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2757 AN: 3466

East Asian (EAS) AF: 0.438 AC: 2268 AN: 5174

South Asian (SAS) AF: 0.745 AC: 3592 AN: 4822

European-Finnish (FIN) AF: 0.806 AC: 8527 AN: 10576

Middle Eastern (MID) AF: 0.842 AC: 246 AN: 292

European-Non Finnish (NFE) AF: 0.782 AC: 53167 AN: 67976

Other (OTH) AF: 0.774 AC: 1635 AN: 2112

Alfa AF: 0.782 Hom.: 25684

Bravo AF: 0.773

Asia WGS AF: 0.611 AC: 2127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.55
PhyloP100		0.078
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: rs2485523; hg19: chr9-104457236;