Variant chr11-120831888-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_014619.5(GRIK4):c.548T>G(p.Leu183Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,686 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: 0.000013 ( 0 hom. )

Consequence

GRIK4
NM_014619.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

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 -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.824

BS2

High AC in GnomAdExome4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK4	NM_014619.5 linkuse as main transcript	c.548T>G	p.Leu183Arg	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.548T>G	p.Leu183Arg	missense_variant	7/21	2	NM_014619.5	ENSP00000435648	P1
GRIK4	ENST00000438375.2 linkuse as main transcript	c.548T>G	p.Leu183Arg	missense_variant	6/20	1		ENSP00000404063	P1
GRIK4	ENST00000533291.5 linkuse as main transcript	n.946T>G		non_coding_transcript_exon_variant	7/18	1
GRIK4	ENST00000638419.1 linkuse as main transcript	c.548T>G	p.Leu183Arg	missense_variant	7/21	5		ENSP00000492086	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461686

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727142

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:

0.0000171

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

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

Feb 15, 2023

The c.548T>G (p.L183R) alteration is located in exon 5 (coding exon 5) of the GRIK4 gene. This alteration results from a T to G substitution at nucleotide position 548, causing the leucine (L) at amino acid position 183 to be replaced by an arginine (R). 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

0.95

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

.;.;D

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.82

D;D;D

MetaSVM

Uncertain

0.013

MutationAssessor

Benign

2.0

M;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.6

N;.;N

REVEL

Uncertain

0.63

Sift

Benign

0.37

T;.;T

Sift4G

Benign

0.67

T;.;T

Polyphen

1.0

D;D;D

Vest4

0.96

MutPred

0.50

Gain of MoRF binding (P = 0.0099);Gain of MoRF binding (P = 0.0099);Gain of MoRF binding (P = 0.0099);

MVP

0.97

MPC

1.6

ClinPred

0.94

GERP RS

4.9

Varity_R

0.45

gMVP

0.91

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