9-101738339-G-A

Variant names:

• chr9-101738339-G-A
• rs1337676
• NM_133445.3:c.-360C>T

Variant summary

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

The NM_133445.3(GRIN3A):​c.-360C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 313,056 control chromosomes in the GnomAD database, including 34,785 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 0.45 (15845 hom., cov: 34)
  • Exomes 𝑓: 0.48 (18940 hom.)
• Consequence: GRIN3A NM_133445.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.493 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.-360C>T		5_prime_UTR	Exon 1 of 9	NP_597702.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN3A	ENST00000361820.6	TSL:1 MANE Select	c.-360C>T		5_prime_UTR	Exon 1 of 9	ENSP00000355155.3
	ENSG00000299588	ENST00000764873.1		n.293-3593G>A		intron	N/A
	ENSG00000299588	ENST00000764874.1		n.127-3593G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68816 AN: 152042 Hom.: 15837 Cov.: 34

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.458

GnomAD4 exome AF: 0.478 AC: 76902 AN: 160898 Hom.: 18940 Cov.: 0 AF XY: 0.476 AC XY: 40849 AN XY: 85832

African (AFR) AF: 0.358 AC: 949 AN: 2650

American (AMR) AF: 0.461 AC: 1749 AN: 3794

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1917 AN: 4358

East Asian (EAS) AF: 0.311 AC: 2068 AN: 6646

South Asian (SAS) AF: 0.455 AC: 11048 AN: 24276

European-Finnish (FIN) AF: 0.523 AC: 4759 AN: 9106

Middle Eastern (MID) AF: 0.423 AC: 309 AN: 730

European-Non Finnish (NFE) AF: 0.498 AC: 49843 AN: 100072

Other (OTH) AF: 0.460 AC: 4260 AN: 9266

GnomAD4 genome AF: 0.452 AC: 68847 AN: 152158 Hom.: 15845 Cov.: 34 AF XY: 0.456 AC XY: 33899 AN XY: 74390

African (AFR) AF: 0.370 AC: 15353 AN: 41540

American (AMR) AF: 0.461 AC: 7044 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1479 AN: 3470

East Asian (EAS) AF: 0.322 AC: 1649 AN: 5128

South Asian (SAS) AF: 0.464 AC: 2239 AN: 4828

European-Finnish (FIN) AF: 0.537 AC: 5694 AN: 10610

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33795 AN: 67978

Other (OTH) AF: 0.461 AC: 971 AN: 2108

Alfa AF: 0.466 Hom.: 2139

Bravo AF: 0.443

Asia WGS AF: 0.378 AC: 1320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.2
DANN	Benign	0.90
PhyloP100		1.1
PromoterAI		0.096	Neutral
Mutation Taster		=300/0	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: rs1337676; hg19: chr9-104500621;