rs10512287

Variant names:

• chr9-101696686-A-G
• rs10512287
• NM_133445.3:c.700-9486T>C

Variant summary

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

The NM_133445.3(GRIN3A):​c.700-9486T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,220 control chromosomes in the GnomAD database, including 1,588 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 0.13 (1588 hom., cov: 32)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 5 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=-0.61).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN3A	NM_133445.3	c.700-9486T>C		intron_variant	Intron 1 of 8	ENST00000361820.6	NP_597702.2
GRIN3A	XM_011518211.3	c.700-9486T>C		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.700-9486T>C		intron_variant	Intron 1 of 8	1	NM_133445.3	ENSP00000355155.3

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19921 AN: 152102 Hom.: 1585 Cov.: 32

Gnomad AFR AF: 0.0342

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.131 AC: 19926 AN: 152220 Hom.: 1588 Cov.: 32 AF XY: 0.130 AC XY: 9677 AN XY: 74436

African (AFR) AF: 0.0342 AC: 1420 AN: 41576

American (AMR) AF: 0.189 AC: 2889 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 572 AN: 3468

East Asian (EAS) AF: 0.168 AC: 870 AN: 5182

South Asian (SAS) AF: 0.138 AC: 663 AN: 4814

European-Finnish (FIN) AF: 0.134 AC: 1425 AN: 10600

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11513 AN: 67970

Other (OTH) AF: 0.145 AC: 306 AN: 2114

Alfa AF: 0.143 Hom.: 332

Bravo AF: 0.135

Asia WGS AF: 0.175 AC: 607 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.79
PhyloP100		0.17
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: rs10512287; hg19: chr9-104458968;