rs41297895

Variant names:

• chr11-120819909-C-A
• rs41297895
• NM_014619.5:c.500C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-120819909-C-A
• chr11-120819909-C-G
• chr11-120819909-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.53

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]

ACMG classification

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
GRIK4	NM_014619.5	c.500C>A	p.Ala167Asp	missense_variant	Exon 6 of 21	ENST00000527524.8	NP_055434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK4	ENST00000527524.8	c.500C>A	p.Ala167Asp	missense_variant	Exon 6 of 21	2	NM_014619.5	ENSP00000435648.2
GRIK4	ENST00000438375.2	c.500C>A	p.Ala167Asp	missense_variant	Exon 5 of 20	1		ENSP00000404063.2
GRIK4	ENST00000533291.5	n.898C>A		non_coding_transcript_exon_variant	Exon 6 of 18	1
GRIK4	ENST00000638419.1	c.500C>A	p.Ala167Asp	missense_variant	Exon 6 of 21	5		ENSP00000492086.1

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

Other links and lift over

dbSNP: rs41297895; hg19: chr11-120690618;