9-101664982-C-G

Variant names:

• chr9-101664982-C-G
• rs7849782
• NM_133445.3:c.2352+5078G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133445.3(GRIN3A):​c.2352+5078G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,498 control chromosomes in the GnomAD database, including 22,548 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 0.55 (22548 hom., cov: 31)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653
• Publications: 5 publications found

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]

ENSG00000299588 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133445.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN3A	NM_133445.3	MANE Select	c.2352+5078G>C		intron	N/A	NP_597702.2	Q8TCU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN3A	ENST00000361820.6	TSL:1 MANE Select	c.2352+5078G>C		intron	N/A	ENSP00000355155.3	Q8TCU5
	ENSG00000299588	ENST00000764873.1		n.223+58607C>G		intron	N/A
	ENSG00000299588	ENST00000764874.1		n.57+14429C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82531 AN: 151378 Hom.: 22527 Cov.: 31

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.545 AC: 82602 AN: 151498 Hom.: 22548 Cov.: 31 AF XY: 0.543 AC XY: 40206 AN XY: 73990

African (AFR) AF: 0.583 AC: 24088 AN: 41338

American (AMR) AF: 0.557 AC: 8449 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1954 AN: 3462

East Asian (EAS) AF: 0.485 AC: 2477 AN: 5112

South Asian (SAS) AF: 0.516 AC: 2484 AN: 4814

European-Finnish (FIN) AF: 0.509 AC: 5351 AN: 10504

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35893 AN: 67798

Other (OTH) AF: 0.560 AC: 1177 AN: 2100

Alfa AF: 0.345 Hom.: 745

Bravo AF: 0.550

Asia WGS AF: 0.555 AC: 1928 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.53
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7849782; hg19: chr9-104427264; COSMIC: COSV62458831;