Genetic Variant GRIK5:p.Val930Leu (chr19-41999026-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002088.5(GRIK5):c.2788G>T(p.Val930Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000435 in 943,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

GRIK5
NM_002088.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.425

Publications

0 publications found

Variant links:

Genes affected

GRIK5 (HGNC:4583): (glutamate ionotropic receptor kainate type subunit 5) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

GRIK5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06505248).

BS2

High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002088.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK5	NM_002088.5	MANE Select	c.2788G>T	p.Val930Leu	missense	Exon 20 of 20	NP_002079.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRIK5	ENST00000593562.6	TSL:5 MANE Select	c.2788G>T	p.Val930Leu	missense	Exon 20 of 20	ENSP00000470251.1	Q16478-1
GRIK5	ENST00000262895.7	TSL:1	c.2788G>T	p.Val930Leu	missense	Exon 19 of 19	ENSP00000262895.2	Q16478-1
GRIK5	ENST00000454993.6	TSL:1	n.1665G>T		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes

AF:

0.0000390

AC:

AN:

128154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00140

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000139

AC:

AN:

14398

AF XY:

0.000227

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000442

AC:

AN:

814848

Hom.:

Cov.:

AF XY:

0.0000455

AC XY:

AN XY:

395958

show subpopulations

African (AFR)

AF:

0.0000602

AC:

AN:

16622

American (AMR)

AF:

0.00

AC:

AN:

9270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11864

East Asian (EAS)

AF:

0.00

AC:

AN:

20202

South Asian (SAS)

AF:

0.00120

AC:

AN:

25866

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19042

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2260

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

677376

Other (OTH)

AF:

0.000124

AC:

AN:

32346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000390

AC:

AN:

128186

Hom.:

Cov.:

AF XY:

0.0000489

AC XY:

AN XY:

61410

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

35336

American (AMR)

AF:

0.00

AC:

AN:

12586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3198

East Asian (EAS)

AF:

0.00

AC:

AN:

3620

South Asian (SAS)

AF:

0.00140

AC:

AN:

3560

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

246

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

60514

Other (OTH)

AF:

0.00

AC:

AN:

1788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.076

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

0.42

PrimateAI

Pathogenic

0.98

PROVEAN

Benign

-0.42

REVEL

Benign

0.023

Sift

Uncertain

0.016

Sift4G

Benign

0.073

Polyphen

0.14

Vest4

0.20

MutPred

0.24

Loss of sheet (P = 0.0817)

MVP

0.25

MPC

0.87

ClinPred

0.16

GERP RS

2.1

Varity_R

0.17

Mutation Taster

=67/33

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over