rs1572560

Positions:

• chr9-101682576-A-G

Variant summary

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

The NM_133445.3(GRIN3A):​c.1304+4020T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,216 control chromosomes in the GnomAD database, including 48,046 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 0.79 (48046 hom., cov: 34)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.854

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN3A	NM_133445.3	c.1304+4020T>C		intron_variant		ENST00000361820.6
GRIN3A	XM_011518211.3	c.1304+4020T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN3A	ENST00000361820.6	c.1304+4020T>C		intron_variant		1	NM_133445.3	P1

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120217 AN: 152098 Hom.: 47991 Cov.: 34

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.791 AC: 120335 AN: 152216 Hom.: 48046 Cov.: 34 AF XY: 0.789 AC XY: 58718 AN XY: 74428

Gnomad4 AFR AF: 0.867

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.780

Alfa AF: 0.788 Hom.: 20562

Bravo AF: 0.783

Asia WGS AF: 0.615 AC: 2141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.85
DANN	Benign	0.36

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: rs1572560; hg19: chr9-104444858;