19-41998982-GGC-CGA

Variant names:

• chr19-41998982-GGC-CGA
• NM_002088.5:c.2830_2832delGCCinsTCG
• GRIK5 p.Ala944Ser

Variant summary

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

The NM_002088.5(GRIK5):​c.2830_2832delGCCinsTCG​(p.Ala944Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. A944T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: GRIK5 NM_002088.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85
• 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.

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.2830_2832delGCCinsTCG	p.Ala944Ser	missense	N/A	NP_002079.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK5	ENST00000593562.6	TSL:5 MANE Select	c.2830_2832delGCCinsTCG	p.Ala944Ser	missense	N/A	ENSP00000470251.1	Q16478-1
	GRIK5	ENST00000262895.7	TSL:1	c.2830_2832delGCCinsTCG	p.Ala944Ser	missense	N/A	ENSP00000262895.2	Q16478-1
	GRIK5	ENST00000454993.6	TSL:1	n.1707_1709delGCCinsTCG		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-42503134;