NM_133445.3:c.1305-5981A>G

Variant names:

• chr9-101677088-T-C
• rs1323423
• NM_133445.3:c.1305-5981A>G

Variant summary

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

The NM_133445.3(GRIN3A):​c.1305-5981A>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 151,680 control chromosomes in the GnomAD database, including 4,465 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 (4465 hom., cov: 31)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133445.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN3A	NM_133445.3	MANE Select	c.1305-5981A>G		intron	N/A	NP_597702.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN3A	ENST00000361820.6	TSL:1 MANE Select	c.1305-5981A>G		intron	N/A	ENSP00000355155.3
	ENSG00000299588	ENST00000764873.1		n.224-47660T>C		intron	N/A
	ENSG00000299588	ENST00000764874.1		n.57+26535T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35407 AN: 151564 Hom.: 4463 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.147

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.234 AC: 35424 AN: 151680 Hom.: 4465 Cov.: 31 AF XY: 0.234 AC XY: 17337 AN XY: 74156

African (AFR) AF: 0.216 AC: 8957 AN: 41442

American (AMR) AF: 0.266 AC: 4050 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3468

East Asian (EAS) AF: 0.563 AC: 2888 AN: 5132

South Asian (SAS) AF: 0.248 AC: 1189 AN: 4804

European-Finnish (FIN) AF: 0.191 AC: 1998 AN: 10440

Middle Eastern (MID) AF: 0.159 AC: 46 AN: 290

European-Non Finnish (NFE) AF: 0.218 AC: 14768 AN: 67858

Other (OTH) AF: 0.237 AC: 498 AN: 2102

Alfa AF: 0.228 Hom.: 12966

Bravo AF: 0.246

Asia WGS AF: 0.393 AC: 1364 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.75
PhyloP100		-0.17
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: rs1323423; hg19: chr9-104439370;