Genetic Variant GRIK3:p.Ser310Thr (chr1-36859876-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000831.4(GRIK3):c.928T>A(p.Ser310Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GRIK3
NM_000831.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.959

Publications

49 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050253093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK3	NM_000831.4 link	c.928T>A	p.Ser310Thr	missense_variant	Exon 6 of 16	ENST00000373091.8	NP_000822.2	Q13003-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK3	ENST00000373091.8 link	c.928T>A	p.Ser310Thr	missense_variant	Exon 6 of 16	1	NM_000831.4	ENSP00000362183.3		Q13003-1
GRIK3	ENST00000373093.4 link	c.928T>A	p.Ser310Thr	missense_variant	Exon 6 of 15	1		ENSP00000362185.4		Q13003-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461634

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727106

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111852

Other (OTH)

AF:

0.00

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

8084

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.085

T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N

PhyloP100

0.96

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.021

Sift

Benign

0.24

T;T

Sift4G

Benign

0.60

T;T

Polyphen

0.0

B;.

Vest4

0.11

MutPred

0.41

Loss of disorder (P = 0.0679);Loss of disorder (P = 0.0679);

MVP

0.19

MPC

0.60

ClinPred

0.084

GERP RS

3.9

Varity_R

0.049

gMVP

0.45

Mutation Taster

=100/0

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

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1-36859876-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over