rs10115450

Variant names:

• chr9-101623591-T-C
• rs10115450
• NM_133445.3:c.2499-158A>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.2499-158A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,098 control chromosomes in the GnomAD database, including 10,664 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 0.37 (10664 hom., cov: 32)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN3A	NM_133445.3	MANE Select	c.2499-158A>G		intron	N/A	NP_597702.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN3A	ENST00000361820.6	TSL:1 MANE Select	c.2499-158A>G		intron	N/A	ENSP00000355155.3
	ENSG00000299588	ENST00000764873.1		n.223+17216T>C		intron	N/A
	ENSG00000299588	ENST00000764875.1		n.198+17216T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55567 AN: 151976 Hom.: 10637 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.366 AC: 55647 AN: 152098 Hom.: 10664 Cov.: 32 AF XY: 0.366 AC XY: 27202 AN XY: 74378

African (AFR) AF: 0.488 AC: 20252 AN: 41472

American (AMR) AF: 0.312 AC: 4765 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1310 AN: 3464

East Asian (EAS) AF: 0.274 AC: 1421 AN: 5178

South Asian (SAS) AF: 0.282 AC: 1363 AN: 4826

European-Finnish (FIN) AF: 0.379 AC: 4016 AN: 10588

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

European-Non Finnish (NFE) AF: 0.314 AC: 21363 AN: 67986

Other (OTH) AF: 0.365 AC: 772 AN: 2114

Alfa AF: 0.335 Hom.: 3885

Bravo AF: 0.361

Asia WGS AF: 0.319 AC: 1110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.4
DANN	Benign	0.57
PhyloP100		-0.043
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: rs10115450; hg19: chr9-104385873; COSMIC: COSV62454563;