9-101640082-A-C

Variant names:

• chr9-101640082-A-C
• rs1016429
• NM_133445.3:c.2353-11681T>G

Variant summary

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

The NM_133445.3(GRIN3A):​c.2353-11681T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,200 control chromosomes in the GnomAD database, including 923 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 0.10 (923 hom., cov: 32)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN3A	NM_133445.3	c.2353-11681T>G		intron_variant	Intron 3 of 8	ENST00000361820.6	NP_597702.2
GRIN3A	XM_011518211.3	c.2353-11681T>G		intron_variant	Intron 3 of 6		XP_011516513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN3A	ENST00000361820.6	c.2353-11681T>G		intron_variant	Intron 3 of 8	1	NM_133445.3	ENSP00000355155.3
ENSG00000299588	ENST00000764873.1	n.223+33707A>C		intron_variant	Intron 2 of 4
ENSG00000299588	ENST00000764875.1	n.198+33707A>C		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15321 AN: 152082 Hom.: 921 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.0861

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0975

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

GnomAD4 genome AF: 0.101 AC: 15350 AN: 152200 Hom.: 923 Cov.: 32 AF XY: 0.103 AC XY: 7629 AN XY: 74398

African (AFR) AF: 0.166 AC: 6905 AN: 41524

American (AMR) AF: 0.0859 AC: 1314 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0865 AC: 300 AN: 3470

East Asian (EAS) AF: 0.0530 AC: 274 AN: 5172

South Asian (SAS) AF: 0.101 AC: 487 AN: 4826

European-Finnish (FIN) AF: 0.101 AC: 1072 AN: 10594

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0668 AC: 4539 AN: 68000

Other (OTH) AF: 0.100 AC: 212 AN: 2114

Alfa AF: 0.0641 Hom.: 230

Bravo AF: 0.101

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.40
PhyloP100		-0.066
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: rs1016429; hg19: chr9-104402364;