rs778828614

Variant summary

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

The NM_017551.3(GRID1):​c.2753G>T​(p.Arg918Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R918Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

GRID1
NM_017551.3 missense

Scores

4
6
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.91
Variant links:
Genes affected
GRID1 (HGNC:4575): (glutamate ionotropic receptor delta type subunit 1) This gene encodes a subunit of glutamate receptor channels. These channels mediate most of the fast excitatory synaptic transmission in the central nervous system and play key roles in synaptic plasticity.[provided by RefSeq, Jan 2009]
GRID1-AS1 (HGNC:44131): (GRID1 antisense RNA 1)

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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 rank MANE Protein UniProt
GRID1NM_017551.3 linkc.2753G>T p.Arg918Leu missense_variant Exon 16 of 16 ENST00000327946.12 NP_060021.1 Q9ULK0-1A8KAN9
GRID1XM_047425122.1 linkc.1466G>T p.Arg489Leu missense_variant Exon 9 of 9 XP_047281078.1
GRID1XM_047425123.1 linkc.1466G>T p.Arg489Leu missense_variant Exon 9 of 9 XP_047281079.1
GRID1-AS1NR_038986.1 linkn.282-2845C>A intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRID1ENST00000327946.12 linkc.2753G>T p.Arg918Leu missense_variant Exon 16 of 16 2 NM_017551.3 ENSP00000330148.7 Q9ULK0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251050
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135766
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.086
T
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.85
D
M_CAP
Benign
0.024
T
MetaRNN
Uncertain
0.51
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
L
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-1.6
N
REVEL
Uncertain
0.34
Sift
Uncertain
0.026
D
Sift4G
Benign
0.096
T
Polyphen
0.99
D
Vest4
0.52
MutPred
0.23
Loss of helix (P = 0.0093);
MVP
0.37
MPC
0.94
ClinPred
0.88
D
GERP RS
5.7
Varity_R
0.25
gMVP
0.55

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: rs778828614; hg19: chr10-87362307; API