Variant 1-36805228-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000373091.8(GRIK3):c.2324A>T(p.Tyr775Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,838 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GRIK3
ENST00000373091.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.95

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK3	NM_000831.4 linkuse as main transcript	c.2324A>T	p.Tyr775Phe	missense_variant	15/16	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.2324A>T	p.Tyr775Phe	missense_variant	15/16	1	NM_000831.4	ENSP00000362183	P1	Q13003-1
GRIK3	ENST00000373093.4 linkuse as main transcript	c.2324A>T	p.Tyr775Phe	missense_variant	15/15	1		ENSP00000362185		Q13003-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457838

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724732

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:

0.00000180

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 09, 2024

The c.2324A>T (p.Y775F) alteration is located in exon 15 (coding exon 15) of the GRIK3 gene. This alteration results from a A to T substitution at nucleotide position 2324, causing the tyrosine (Y) at amino acid position 775 to be replaced by a phenylalanine (F). 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

Benign

0.13

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.40

T;.

Eigen

Benign

-0.061

Eigen_PC

Benign

0.089

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.0062

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.21

Sift

Benign

0.11

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.034

B;.

Vest4

0.70

MutPred

0.68

Loss of catalytic residue at Y775 (P = 0.0687);Loss of catalytic residue at Y775 (P = 0.0687);

MVP

0.54

MPC

0.81

ClinPred

0.92

GERP RS

3.9

Varity_R

0.50

gMVP

0.81

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

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