9-101664982-C-G

Variant summary

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

The NM_133445.3(GRIN3A):c.2352+5078G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,498 control chromosomes in the GnomAD database, including 22,548 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 0.55 (22548 hom., cov: 31)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN3A	NM_133445.3	c.2352+5078G>C		intron_variant		ENST00000361820.6
GRIN3A	XM_011518211.3	c.2352+5078G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN3A	ENST00000361820.6	c.2352+5078G>C		intron_variant		1	NM_133445.3	P1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82531 AN: 151378 Hom.: 22527 Cov.: 31

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.545 AC: 82602 AN: 151498 Hom.: 22548 Cov.: 31 AF XY: 0.543 AC XY: 40206 AN XY: 73990

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.560

Alfa AF: 0.345 Hom.: 745

Bravo AF: 0.550

Asia WGS AF: 0.555 AC: 1928 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.64
Dann	Benign	0.53

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: rs7849782; hg19: chr9-104427264; COSMIC: COSV62458831;