chr9-101585868-G-A

Variant names:

• chr9-101585868-G-A
• rs11788456
• NM_133445.3:c.2767-6508C>T

Variant summary

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

The NM_133445.3(GRIN3A):​c.2767-6508C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,954 control chromosomes in the GnomAD database, including 22,368 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 0.54 (22368 hom., cov: 31)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.735
• Publications: 9 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN3A	NM_133445.3	c.2767-6508C>T		intron_variant	Intron 6 of 8	ENST00000361820.6	NP_597702.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN3A	ENST00000361820.6	c.2767-6508C>T		intron_variant	Intron 6 of 8	1	NM_133445.3	ENSP00000355155.3

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82084 AN: 151836 Hom.: 22334 Cov.: 31

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.541 AC: 82170 AN: 151954 Hom.: 22368 Cov.: 31 AF XY: 0.536 AC XY: 39834 AN XY: 74298

African (AFR) AF: 0.547 AC: 22662 AN: 41412

American (AMR) AF: 0.534 AC: 8161 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2055 AN: 3472

East Asian (EAS) AF: 0.359 AC: 1853 AN: 5168

South Asian (SAS) AF: 0.496 AC: 2388 AN: 4816

European-Finnish (FIN) AF: 0.516 AC: 5447 AN: 10558

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

European-Non Finnish (NFE) AF: 0.554 AC: 37638 AN: 67936

Other (OTH) AF: 0.548 AC: 1157 AN: 2112

Alfa AF: 0.546 Hom.: 38003

Bravo AF: 0.540

Asia WGS AF: 0.497 AC: 1732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.5
DANN	Benign	0.57
PhyloP100		0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11788456; hg19: chr9-104348150; COSMIC: COSV62451984;