rs17189632

Positions:

• chr9-101605720-T-A
• chr9-101605720-T-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+7656A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,066 control chromosomes in the GnomAD database, including 13,047 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 0.41 (13047 hom., cov: 32)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN3A	NM_133445.3	c.2766+7656A>T		intron_variant		ENST00000361820.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN3A	ENST00000361820.6	c.2766+7656A>T		intron_variant		1	NM_133445.3	P1
GRIN3A	ENST00000479772.1	n.148-2686A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62198 AN: 151948 Hom.: 13042 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.409 AC: 62229 AN: 152066 Hom.: 13047 Cov.: 32 AF XY: 0.410 AC XY: 30514 AN XY: 74336

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.392

Alfa AF: 0.456 Hom.: 2006

Bravo AF: 0.398

Asia WGS AF: 0.339 AC: 1178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.73

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: rs17189632; hg19: chr9-104368002; COSMIC: COSV62451999;