9-101676642-T-C

Position:

• chr9-101676642-T-C

Variant summary

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

The NM_133445.3(GRIN3A):​c.1305-5535A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 151,782 control chromosomes in the GnomAD database, including 4,466 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 0.23 (4466 hom., cov: 32)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47

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 (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN3A	NM_133445.3	c.1305-5535A>G		intron_variant		ENST00000361820.6
GRIN3A	XM_011518211.3	c.1305-5535A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN3A	ENST00000361820.6	c.1305-5535A>G		intron_variant		1	NM_133445.3	P1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35436 AN: 151664 Hom.: 4463 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.234 AC: 35455 AN: 151782 Hom.: 4466 Cov.: 32 AF XY: 0.234 AC XY: 17368 AN XY: 74200

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.236

Alfa AF: 0.213 Hom.: 488

Bravo AF: 0.246

Asia WGS AF: 0.393 AC: 1359 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.49

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: rs1323426; hg19: chr9-104438924;