Variant chr1-36804959-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000373093.4(GRIK3):c.2593A>G(p.Arg865Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00768 in 1,611,884 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0079 ( 68 hom. )

Consequence

GRIK3
ENST00000373093.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.62

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004658401).

BP6

Variant 1-36804959-T-C is Benign according to our data. Variant chr1-36804959-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2638675.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 833 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK3	NM_000831.4 linkuse as main transcript	c.2565+28A>G		intron_variant		ENST00000373091.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK3	ENST00000373093.4 linkuse as main transcript	c.2593A>G	p.Arg865Gly	missense_variant	15/15	1			Q13003-2
GRIK3	ENST00000373091.8 linkuse as main transcript	c.2565+28A>G		intron_variant		1	NM_000831.4	P1	Q13003-1

Frequencies

GnomAD3 genomes

AF:

0.00547

AC:

833

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00976

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00474

AC:

1178

AN:

248262

Hom.:

AF XY:

0.00476

AC XY:

640

AN XY:

134438

show subpopulations

Gnomad AFR exome

AF:

0.00194

Gnomad AMR exome

AF:

0.00221

Gnomad ASJ exome

AF:

0.00404

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000888

Gnomad FIN exome

AF:

0.00190

Gnomad NFE exome

AF:

0.00847

Gnomad OTH exome

AF:

0.00296

GnomAD4 exome

AF:

0.00791

AC:

11552

AN:

1459564

Hom.:

Cov.:

AF XY:

0.00759

AC XY:

5512

AN XY:

725840

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00218

Gnomad4 ASJ exome

AF:

0.00381

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000988

Gnomad4 FIN exome

AF:

0.00197

Gnomad4 NFE exome

AF:

0.00962

Gnomad4 OTH exome

AF:

0.00728

GnomAD4 genome

AF:

0.00547

AC:

833

AN:

152320

Hom.:

Cov.:

AF XY:

0.00477

AC XY:

355

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00976

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00751

Hom.:

Bravo

AF:

0.00536

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.0130

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0109

AC:

ExAC

AF:

0.00486

AC:

590

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00818

EpiControl

AF:

0.00806

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

GRIK3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.37

DANN

Benign

0.86

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0047

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-0.48

REVEL

Benign

0.034

Sift

Benign

0.070

Vest4

0.051

MVP

0.068

ClinPred

0.00069

GERP RS

-3.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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