Variant 19-41999247-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002088.5(GRIK5):c.2567G>T(p.Arg856Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,372,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

GRIK5
NM_002088.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10

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:

GRIK5 (HGNC:):

GRIK5 links:

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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=0.1879521).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK5	NM_002088.5 linkuse as main transcript	c.2567G>T	p.Arg856Leu	missense_variant	20/20	ENST00000593562.6	NP_002079.3	Q16478-1
GRIK5	XM_011526862.3 linkuse as main transcript	c.2570G>T	p.Arg857Leu	missense_variant	20/20		XP_011525164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GRIK5	ENST00000593562.6 linkuse as main transcript	c.2567G>T	p.Arg856Leu	missense_variant	20/20	5	NM_002088.5	ENSP00000470251.1	Q16478-1
GRIK5	ENST00000262895.7 linkuse as main transcript	c.2567G>T	p.Arg856Leu	missense_variant	19/19	1		ENSP00000262895.2	Q16478-1
GRIK5	ENST00000454993.6 linkuse as main transcript	n.1444G>T		non_coding_transcript_exon_variant	9/9	1
GRIK5	ENST00000602210.1 linkuse as main transcript	n.385G>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000146

AC:

AN:

1372456

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

677192

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:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.30e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2024

The c.2567G>T (p.R856L) alteration is located in exon 19 (coding exon 19) of the GRIK5 gene. This alteration results from a G to T substitution at nucleotide position 2567, causing the arginine (R) at amino acid position 856 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

T;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.081

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.91

.;D

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;L

PrimateAI

Pathogenic

0.95

PROVEAN

Uncertain

-2.5

N;.

REVEL

Benign

0.031

Sift

Uncertain

0.025

D;.

Sift4G

Uncertain

0.043

D;D

Polyphen

0.49

P;P

Vest4

0.34

MutPred

0.31

Loss of methylation at K857 (P = 0.0469);Loss of methylation at K857 (P = 0.0469);

MVP

0.24

MPC

1.3

ClinPred

0.57

GERP RS

3.0

Varity_R

0.29

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over