rs10512285

Positions:

• chr9-101670752-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_133445.3(GRIN3A):​c.1660T>C​(p.Leu554=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,613,574 control chromosomes in the GnomAD database, including 122,987 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 0.33 (9450 hom., cov: 33)
  • Exomes 𝑓: 0.39 (113537 hom.)
• Consequence: GRIN3A NM_133445.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.146 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN3A	NM_133445.3	c.1660T>C	p.Leu554=	synonymous_variant	3/9	ENST00000361820.6	NP_597702.2
GRIN3A	XM_011518211.3	c.1660T>C	p.Leu554=	synonymous_variant	3/7		XP_011516513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN3A	ENST00000361820.6	c.1660T>C	p.Leu554=	synonymous_variant	3/9	1	NM_133445.3	ENSP00000355155	P1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50898 AN: 152020 Hom.: 9445 Cov.: 33

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.364

GnomAD3 exomes AF: 0.365 AC: 91639 AN: 251034 Hom.: 17467 AF XY: 0.368 AC XY: 49876 AN XY: 135666

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.379

Gnomad ASJ exome AF: 0.422

Gnomad EAS exome AF: 0.208

Gnomad SAS exome AF: 0.321

Gnomad FIN exome AF: 0.391

Gnomad NFE exome AF: 0.414

Gnomad OTH exome AF: 0.397

GnomAD4 exome AF: 0.390 AC: 569668 AN: 1461436 Hom.: 113537 Cov.: 38 AF XY: 0.389 AC XY: 282751 AN XY: 727034

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.379

Gnomad4 ASJ exome AF: 0.417

Gnomad4 EAS exome AF: 0.189

Gnomad4 SAS exome AF: 0.319

Gnomad4 FIN exome AF: 0.388

Gnomad4 NFE exome AF: 0.409

Gnomad4 OTH exome AF: 0.382

GnomAD4 genome AF: 0.335 AC: 50922 AN: 152138 Hom.: 9450 Cov.: 33 AF XY: 0.332 AC XY: 24683 AN XY: 74372

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.364

Alfa AF: 0.397 Hom.: 24350

Bravo AF: 0.329

Asia WGS AF: 0.308 AC: 1070 AN: 3478

EpiCase AF: 0.406

EpiControl AF: 0.408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.25
DANN	Benign	0.48

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: rs10512285; hg19: chr9-104433034; COSMIC: COSV62450870;