rs10121600

Positions:

• chr9-101615721-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133445.3(GRIN3A):​c.2615-2194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,974 control chromosomes in the GnomAD database, including 12,164 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 0.39 (12164 hom., cov: 31)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN3A	NM_133445.3	c.2615-2194G>A		intron_variant		ENST00000361820.6
GRIN3A	XM_011518211.3	c.2615-2194G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN3A	ENST00000361820.6	c.2615-2194G>A		intron_variant		1	NM_133445.3	P1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59063 AN: 151856 Hom.: 12121 Cov.: 31

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.389 AC: 59164 AN: 151974 Hom.: 12164 Cov.: 31 AF XY: 0.386 AC XY: 28635 AN XY: 74258

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.381

Alfa AF: 0.340 Hom.: 8180

Bravo AF: 0.390

Asia WGS AF: 0.357 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.69

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: rs10121600; hg19: chr9-104378003;