rs1016429

Positions:

• chr9-101640082-A-C
• chr9-101640082-A-G

Variant summary

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

The NM_133445.3(GRIN3A):​c.2353-11681T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,200 control chromosomes in the GnomAD database, including 923 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 0.10 (923 hom., cov: 32)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN3A	NM_133445.3	c.2353-11681T>G		intron_variant		ENST00000361820.6	NP_597702.2
GRIN3A	XM_011518211.3	c.2353-11681T>G		intron_variant			XP_011516513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN3A	ENST00000361820.6	c.2353-11681T>G		intron_variant		1	NM_133445.3	ENSP00000355155	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15321 AN: 152082 Hom.: 921 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.0861

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0975

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

GnomAD4 genome AF: 0.101 AC: 15350 AN: 152200 Hom.: 923 Cov.: 32 AF XY: 0.103 AC XY: 7629 AN XY: 74398

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.0859

Gnomad4 ASJ AF: 0.0865

Gnomad4 EAS AF: 0.0530

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0668

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0624 Hom.: 201

Bravo AF: 0.101

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.40

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: rs1016429; hg19: chr9-104402364;