rs4743484

Positions:

• chr9-101717198-C-T

Variant summary

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

The NM_133445.3(GRIN3A):​c.699+20083G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,092 control chromosomes in the GnomAD database, including 2,488 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 0.16 (2488 hom., cov: 32)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN3A	NM_133445.3	c.699+20083G>A		intron_variant		ENST00000361820.6	NP_597702.2
GRIN3A	XM_011518211.3	c.699+20083G>A		intron_variant			XP_011516513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN3A	ENST00000361820.6	c.699+20083G>A		intron_variant		1	NM_133445.3	ENSP00000355155.3

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24643 AN: 151972 Hom.: 2491 Cov.: 32

Gnomad AFR AF: 0.0463

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0461

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.162 AC: 24643 AN: 152092 Hom.: 2488 Cov.: 32 AF XY: 0.163 AC XY: 12083 AN XY: 74326

Gnomad4 AFR AF: 0.0462

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.0462

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.184

Alfa AF: 0.209 Hom.: 1690

Bravo AF: 0.149

Asia WGS AF: 0.116 AC: 402 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	5.1
DANN	Benign	0.26

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: rs4743484; hg19: chr9-104479480;