chr9-101716645-C-G

Position:

• chr9-101716645-C-G

Variant summary

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

The NM_133445.3(GRIN3A):​c.699+20636G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,534 control chromosomes in the GnomAD database, including 13,853 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 0.43 (13853 hom., cov: 32)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN3A	NM_133445.3	c.699+20636G>C		intron_variant		ENST00000361820.6	NP_597702.2
GRIN3A	XM_011518211.3	c.699+20636G>C		intron_variant			XP_011516513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN3A	ENST00000361820.6	c.699+20636G>C		intron_variant		1	NM_133445.3	ENSP00000355155	P1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64419 AN: 151416 Hom.: 13848 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.425 AC: 64443 AN: 151534 Hom.: 13853 Cov.: 32 AF XY: 0.428 AC XY: 31660 AN XY: 74018

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.433

Alfa AF: 0.442 Hom.: 1797

Bravo AF: 0.423

Asia WGS AF: 0.388 AC: 1353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
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: rs1337697; hg19: chr9-104478927;