Variant chr1-36841757-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000831.4(GRIK3):c.1509G>T(p.Met503Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

GRIK3
NM_000831.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.69

Variant links:

Genes affected

GRIK3 (HGNC:4581): (glutamate ionotropic receptor kainate type subunit 3) Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. It is not certain if the subunit encoded by this gene is subject to RNA editing as the other 2 family members (GRIK1 and GRIK2). A Ser310Ala polymorphism has been associated with schizophrenia, and there are conflicting reports of its association with the pathogenesis of delirium tremens in alcoholics. [provided by RefSeq, Jul 2008]

GRIK3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK3	NM_000831.4 linkuse as main transcript	c.1509G>T	p.Met503Ile	missense_variant	10/16	ENST00000373091.8	NP_000822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK3	ENST00000373091.8 linkuse as main transcript	c.1509G>T	p.Met503Ile	missense_variant	10/16	1	NM_000831.4	ENSP00000362183	P1	Q13003-1
GRIK3	ENST00000373093.4 linkuse as main transcript	c.1509G>T	p.Met503Ile	missense_variant	10/15	1		ENSP00000362185		Q13003-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251336

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727218

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:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jan 06, 2023

The c.1509G>T (p.M503I) alteration is located in exon 10 (coding exon 10) of the GRIK3 gene. This alteration results from a G to T substitution at nucleotide position 1509, causing the methionine (M) at amino acid position 503 to be replaced by an isoleucine (I). 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

Pathogenic

0.61

BayesDel_addAF

Benign

0.0061

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;.

Eigen

Benign

-0.015

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-0.44

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.1

N;N

REVEL

Uncertain

0.33

Sift

Benign

0.29

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.029

B;.

Vest4

0.54

MutPred

0.77

Loss of catalytic residue at M503 (P = 0.0013);Loss of catalytic residue at M503 (P = 0.0013);

MVP

0.50

MPC

0.77

ClinPred

0.48

GERP RS

4.9

Varity_R

0.39

gMVP

0.95

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over