rs11788456

Positions:

• chr9-101585868-G-A

Variant summary

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

The NM_133445.3(GRIN3A):​c.2767-6508C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,954 control chromosomes in the GnomAD database, including 22,368 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 0.54 (22368 hom., cov: 31)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.735

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN3A	NM_133445.3	c.2767-6508C>T		intron_variant		ENST00000361820.6	NP_597702.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN3A	ENST00000361820.6	c.2767-6508C>T		intron_variant		1	NM_133445.3	ENSP00000355155.3

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82084 AN: 151836 Hom.: 22334 Cov.: 31

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.541 AC: 82170 AN: 151954 Hom.: 22368 Cov.: 31 AF XY: 0.536 AC XY: 39834 AN XY: 74298

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.548

Alfa AF: 0.558 Hom.: 4962

Bravo AF: 0.540

Asia WGS AF: 0.497 AC: 1732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.5
DANN	Benign	0.57

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: rs11788456; hg19: chr9-104348150; COSMIC: COSV62451984;