rs7030238

Positions:

• chr9-101570213-A-C

Variant summary

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

The NM_133445.3(GRIN3A):​c.*2961T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,998 control chromosomes in the GnomAD database, including 4,868 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 0.25 (4867 hom., cov: 32)
  • Exomes 𝑓: 0.20 (1 hom.)
• Consequence: GRIN3A NM_133445.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN3A	NM_133445.3	c.*2961T>G		3_prime_UTR_variant	9/9	ENST00000361820.6	NP_597702.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN3A	ENST00000361820.6	c.*2961T>G		3_prime_UTR_variant	9/9	1	NM_133445.3	ENSP00000355155.3

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37771 AN: 151814 Hom.: 4868 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.197 AC: 13 AN: 66 Hom.: 1 Cov.: 0 AF XY: 0.114 AC XY: 5 AN XY: 44

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.249 AC: 37781 AN: 151932 Hom.: 4867 Cov.: 32 AF XY: 0.243 AC XY: 18067 AN XY: 74246

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.254

Alfa AF: 0.232 Hom.: 2073

Bravo AF: 0.262

Asia WGS AF: 0.225 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.86
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7030238; hg19: chr9-104332495; COSMIC: COSV62451955;