rs3739722

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_133445.3(GRIN3A):​c.3122G>T​(p.Arg1041Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 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. R1041W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GRIN3A
NM_133445.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.97
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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06846422).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRIN3ANM_133445.3 linkc.3122G>T p.Arg1041Leu missense_variant Exon 9 of 9 ENST00000361820.6 NP_597702.2 Q8TCU5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRIN3AENST00000361820.6 linkc.3122G>T p.Arg1041Leu missense_variant Exon 9 of 9 1 NM_133445.3 ENSP00000355155.3 Q8TCU5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461784
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727186
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
AC:
2
AN:
33470
Gnomad4 AMR exome
AF:
0.00
AC:
0
AN:
44720
Gnomad4 ASJ exome
AF:
0.00
AC:
0
AN:
26132
Gnomad4 EAS exome
AF:
0.00
AC:
0
AN:
39696
Gnomad4 SAS exome
AF:
0.00
AC:
0
AN:
86250
Gnomad4 FIN exome
AF:
0.00
AC:
0
AN:
53418
Gnomad4 NFE exome
AF:
0.00
AC:
0
AN:
1111942
Gnomad4 Remaining exome
AF:
0.00
AC:
0
AN:
60388
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
1.0
DANN
Benign
0.96
DEOGEN2
Benign
0.016
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.047
N
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.0061
T
MetaRNN
Benign
0.068
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.18
T
PROVEAN
Benign
-0.84
N
REVEL
Benign
0.069
Sift
Benign
0.10
T
Sift4G
Benign
0.41
T
Polyphen
0.029
B
Vest4
0.094
MutPred
0.45
Loss of sheet (P = 0.0126);
MVP
0.51
MPC
0.17
ClinPred
0.10
T
GERP RS
-4.0
Varity_R
0.047
gMVP
0.21
Mutation Taster
=95/5
polymorphism

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: rs3739722; hg19: chr9-104335682; API