9-101649154-C-T

Variant names:

• chr9-101649154-C-T
• rs1323427
• NM_133445.3:c.2353-20753G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133445.3(GRIN3A):​c.2353-20753G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,906 control chromosomes in the GnomAD database, including 3,206 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 0.19 (3206 hom., cov: 32)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376
• Publications: 5 publications found

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]

ENSG00000299588 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN3A	NM_133445.3	c.2353-20753G>A		intron_variant	Intron 3 of 8	ENST00000361820.6	NP_597702.2
GRIN3A	XM_011518211.3	c.2353-20753G>A		intron_variant	Intron 3 of 6		XP_011516513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN3A	ENST00000361820.6	c.2353-20753G>A		intron_variant	Intron 3 of 8	1	NM_133445.3	ENSP00000355155.3
ENSG00000299588	ENST00000764873.1	n.223+42779C>T		intron_variant	Intron 2 of 4
ENSG00000299588	ENST00000764875.1	n.198+42779C>T		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29329 AN: 151788 Hom.: 3208 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0782

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0473

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.193 AC: 29334 AN: 151906 Hom.: 3206 Cov.: 32 AF XY: 0.192 AC XY: 14250 AN XY: 74250

African (AFR) AF: 0.106 AC: 4402 AN: 41478

American (AMR) AF: 0.199 AC: 3031 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 933 AN: 3462

East Asian (EAS) AF: 0.0475 AC: 244 AN: 5142

South Asian (SAS) AF: 0.171 AC: 822 AN: 4820

European-Finnish (FIN) AF: 0.250 AC: 2642 AN: 10562

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16682 AN: 67902

Other (OTH) AF: 0.209 AC: 440 AN: 2106

Alfa AF: 0.116 Hom.: 273

Bravo AF: 0.182

Asia WGS AF: 0.128 AC: 444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.4
DANN	Benign	0.58
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1323427; hg19: chr9-104411436;