rs41297895

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_014619.5(GRIK4):​c.500C>A​(p.Ala167Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. A167G) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

GRIK4
NM_014619.5 missense

Scores

6
6
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.53
Variant links:
Genes affected
GRIK4 (HGNC:4582): (glutamate ionotropic receptor kainate type subunit 4) This gene encodes a protein that belongs to the glutamate-gated ionic channel family. Glutamate functions as the major excitatory neurotransmitter in the central nervous system through activation of ligand-gated ion channels and G protein-coupled membrane receptors. The protein encoded by this gene forms functional heteromeric kainate-preferring ionic channels with the subunits encoded by related gene family members. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.83

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRIK4NM_014619.5 linkc.500C>A p.Ala167Asp missense_variant Exon 6 of 21 ENST00000527524.8 NP_055434.2 Q16099A0A8D9PH79

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRIK4ENST00000527524.8 linkc.500C>A p.Ala167Asp missense_variant Exon 6 of 21 2 NM_014619.5 ENSP00000435648.2 Q16099
GRIK4ENST00000438375.2 linkc.500C>A p.Ala167Asp missense_variant Exon 5 of 20 1 ENSP00000404063.2 Q16099
GRIK4ENST00000533291.5 linkn.898C>A non_coding_transcript_exon_variant Exon 6 of 18 1
GRIK4ENST00000638419.1 linkc.500C>A p.Ala167Asp missense_variant Exon 6 of 21 5 ENSP00000492086.1 Q16099

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.26
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.079
T;T;T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.89
.;.;D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.83
D;D;D
MetaSVM
Benign
-0.29
T
MutationAssessor
Benign
1.2
L;L;L
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
0.33
N;.;N
REVEL
Uncertain
0.61
Sift
Benign
0.44
T;.;T
Sift4G
Benign
0.56
T;.;T
Polyphen
1.0
D;D;D
Vest4
0.95
MutPred
0.58
Gain of ubiquitination at K168 (P = 0.1235);Gain of ubiquitination at K168 (P = 0.1235);Gain of ubiquitination at K168 (P = 0.1235);
MVP
0.70
MPC
1.6
ClinPred
0.94
D
GERP RS
4.7
Varity_R
0.28
gMVP
0.86

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: rs41297895; hg19: chr11-120690618; API