NM_002088.5:c.2816T>G

Variant names:

• chr19-41998998-A-C
• NM_002088.5:c.2816T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002088.5(GRIK5):​c.2816T>G​(p.Ile939Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: GRIK5 NM_002088.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.67
• Publications: 0 publications found

Genes affected

GRIK5 (HGNC:4583): (glutamate ionotropic receptor kainate type subunit 5) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

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=0.16742194).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002088.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK5	NM_002088.5	MANE Select	c.2816T>G	p.Ile939Ser	missense	Exon 20 of 20	NP_002079.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK5	ENST00000593562.6	TSL:5 MANE Select	c.2816T>G	p.Ile939Ser	missense	Exon 20 of 20	ENSP00000470251.1	Q16478-1
	GRIK5	ENST00000262895.7	TSL:1	c.2816T>G	p.Ile939Ser	missense	Exon 19 of 19	ENSP00000262895.2	Q16478-1
	GRIK5	ENST00000454993.6	TSL:1	n.1693T>G		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.079
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		5.7
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.19
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.013	D
Polyphen		0.28	B
Vest4		0.41
MutPred		0.25		Gain of phosphorylation at I939 (P = 0.0535)
MVP		0.30
MPC		1.4
ClinPred		0.71	D
GERP RS		2.2
Varity_R		0.20
Mutation Taster		=75/25	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

Other links and lift over

hg19: chr19-42503150;