rs1323432

Positions:

• chr9-101600655-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133445.3(GRIN3A):​c.2766+12721T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0806 in 152,210 control chromosomes in the GnomAD database, including 587 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 0.081 (587 hom., cov: 32)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN3A	NM_133445.3	c.2766+12721T>C		intron_variant		ENST00000361820.6	NP_597702.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN3A	ENST00000361820.6	c.2766+12721T>C		intron_variant		1	NM_133445.3	ENSP00000355155	P1

Frequencies

GnomAD3 genomes AF: 0.0807 AC: 12267 AN: 152092 Hom.: 587 Cov.: 32

Gnomad AFR AF: 0.0396

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0938

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0446

Gnomad FIN AF: 0.0893

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0910

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

GnomAD4 genome AF: 0.0806 AC: 12264 AN: 152210 Hom.: 587 Cov.: 32 AF XY: 0.0792 AC XY: 5897 AN XY: 74420

Gnomad4 AFR AF: 0.0394

Gnomad4 AMR AF: 0.0936

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0440

Gnomad4 FIN AF: 0.0893

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0905

Alfa AF: 0.106 Hom.: 907

Bravo AF: 0.0820

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.7
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs1323432; hg19: chr9-104362937;