rs10989591

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_133445.3(GRIN3A):​c.1084G>T​(p.Val362Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V362M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

GRIN3A
NM_133445.3 missense

Scores

2
8
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.05
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GRIN3ANM_133445.3 linkuse as main transcriptc.1084G>T p.Val362Leu missense_variant 2/9 ENST00000361820.6 NP_597702.2 Q8TCU5
GRIN3AXM_011518211.3 linkuse as main transcriptc.1084G>T p.Val362Leu missense_variant 2/7 XP_011516513.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GRIN3AENST00000361820.6 linkuse as main transcriptc.1084G>T p.Val362Leu missense_variant 2/91 NM_133445.3 ENSP00000355155.3 Q8TCU5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251098
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135692
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461790
Hom.:
0
Cov.:
54
AF XY:
0.00000825
AC XY:
6
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.61
BayesDel_addAF
Uncertain
0.016
T
BayesDel_noAF
Benign
-0.13
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.040
T
Eigen
Benign
0.075
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.73
T
M_CAP
Uncertain
0.092
D
MetaRNN
Uncertain
0.45
T
MetaSVM
Uncertain
-0.27
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
8.9e-7
P
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-0.77
N
REVEL
Uncertain
0.32
Sift
Benign
0.080
T
Sift4G
Benign
0.51
T
Polyphen
0.0030
B
Vest4
0.29
MutPred
0.25
Gain of loop (P = 0.0851);
MVP
0.78
MPC
0.12
ClinPred
0.36
T
GERP RS
5.8
Varity_R
0.24
gMVP
0.60

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10989591; hg19: chr9-104449098; API