Variant 11-120831942-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP3BS2

The NM_014619.5(GRIK4):c.602C>T(p.Thr201Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

GRIK4
NM_014619.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.56

Variant links:

Genes affected

GRIK4 (HGNC:4582): (glutamate ionotropic receptor kainate type subunit 4) 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

GRIK4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.837

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK4	NM_014619.5 linkuse as main transcript	c.602C>T	p.Thr201Ile	missense_variant	7/21	ENST00000527524.8	NP_055434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GRIK4	ENST00000527524.8 linkuse as main transcript	c.602C>T	p.Thr201Ile	missense_variant	7/21	2	NM_014619.5	ENSP00000435648	P1
GRIK4	ENST00000438375.2 linkuse as main transcript	c.602C>T	p.Thr201Ile	missense_variant	6/20	1		ENSP00000404063	P1
GRIK4	ENST00000533291.5 linkuse as main transcript	n.1000C>T		non_coding_transcript_exon_variant	7/18	1
GRIK4	ENST00000638419.1 linkuse as main transcript	c.602C>T	p.Thr201Ile	missense_variant	7/21	5		ENSP00000492086	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000360

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

Dec 03, 2021

The c.602C>T (p.T201I) alteration is located in exon 5 (coding exon 5) of the GRIK4 gene. This alteration results from a C to T substitution at nucleotide position 602, causing the threonine (T) at amino acid position 201 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

0.59

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.32

T;T;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

.;.;D

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.84

D;D;D

MetaSVM

Uncertain

0.47

MutationAssessor

Uncertain

2.1

M;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.0

D;.;D

REVEL

Pathogenic

0.75

Sift

Uncertain

0.014

D;.;D

Sift4G

Uncertain

0.058

T;.;T

Polyphen

1.0

D;D;D

Vest4

0.83

MutPred

0.45

Loss of phosphorylation at T201 (P = 0.0137);Loss of phosphorylation at T201 (P = 0.0137);Loss of phosphorylation at T201 (P = 0.0137);

MVP

0.70

MPC

1.4

ClinPred

0.99

GERP RS

4.8

Varity_R

0.32

gMVP

0.75

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