Genetic Variant NM_002088.5:c.2644G>C (chr19-41999170-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002088.5(GRIK5):c.2644G>C(p.Glu882Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,355,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. E882K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

GRIK5
NM_002088.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.34

Variant links:

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]

GRIK5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24129182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK5	NM_002088.5 link	c.2644G>C	p.Glu882Gln	missense_variant	Exon 20 of 20	ENST00000593562.6	NP_002079.3	Q16478-1
GRIK5	XM_011526862.3 link	c.2647G>C	p.Glu883Gln	missense_variant	Exon 20 of 20		XP_011525164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GRIK5	ENST00000593562.6 link	c.2644G>C	p.Glu882Gln	missense_variant	Exon 20 of 20	5	NM_002088.5	ENSP00000470251.1	Q16478-1
GRIK5	ENST00000262895.7 link	c.2644G>C	p.Glu882Gln	missense_variant	Exon 19 of 19	1		ENSP00000262895.2	Q16478-1
GRIK5	ENST00000454993.6 link	n.1521G>C		non_coding_transcript_exon_variant	Exon 9 of 9	1
GRIK5	ENST00000602210.1 link	n.*73G>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.38e-7

AC:

AN:

1355118

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

668768

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.36e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.093

T;T

Eigen

Benign

-0.079

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.91

.;D

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.55

N;.

REVEL

Benign

0.039

Sift

Benign

0.090

T;.

Sift4G

Benign

0.46

T;T

Polyphen

0.87

P;P

Vest4

0.15

MutPred

0.22

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);

MVP

0.50

MPC

1.4

ClinPred

0.61

GERP RS

2.5

Varity_R

0.23

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over