rs1337676

Positions:

• chr9-101738339-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.-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

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN3A	NM_133445.3	c.-360C>T		5_prime_UTR_variant	1/9	ENST00000361820.6
GRIN3A	XM_011518211.3	c.-360C>T		5_prime_UTR_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN3A	ENST00000361820.6	c.-360C>T		5_prime_UTR_variant	1/9	1	NM_133445.3	P1

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

Gnomad4 AFR exome AF: 0.358

Gnomad4 AMR exome AF: 0.461

Gnomad4 ASJ exome AF: 0.440

Gnomad4 EAS exome AF: 0.311

Gnomad4 SAS exome AF: 0.455

Gnomad4 FIN exome AF: 0.523

Gnomad4 NFE exome AF: 0.498

Gnomad4 OTH exome AF: 0.460

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

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.461

Alfa AF: 0.469 Hom.: 2072

Bravo AF: 0.443

Asia WGS AF: 0.378 AC: 1320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.2
DANN	Benign	0.90

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: rs1337676; hg19: chr9-104500621;