rs12342026

Positions:

• chr9-101571582-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.*1592C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,074 control chromosomes in the GnomAD database, including 4,630 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 0.24 (4629 hom., cov: 32)
  • Exomes 𝑓: 0.17 (1 hom.)
• Consequence: GRIN3A NM_133445.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN3A	NM_133445.3	c.*1592C>T		3_prime_UTR_variant	9/9	ENST00000361820.6	NP_597702.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN3A	ENST00000361820.6	c.*1592C>T		3_prime_UTR_variant	9/9	1	NM_133445.3	ENSP00000355155	P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36920 AN: 151914 Hom.: 4629 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.167 AC: 7 AN: 42 Hom.: 1 Cov.: 0 AF XY: 0.176 AC XY: 6 AN XY: 34

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.243 AC: 36942 AN: 152032 Hom.: 4629 Cov.: 32 AF XY: 0.238 AC XY: 17692 AN XY: 74322

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.248

Alfa AF: 0.232 Hom.: 616

Bravo AF: 0.255

Asia WGS AF: 0.223 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.33

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: rs12342026; hg19: chr9-104333864;