19-41998998-A-C

Position:

• chr19-41998998-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002088.5(GRIK5):​c.2816T>G​(p.Ile939Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: GRIK5 NM_002088.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.67

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16742194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK5	NM_002088.5	c.2816T>G	p.Ile939Ser	missense_variant	20/20	ENST00000593562.6	NP_002079.3
GRIK5	XM_011526862.3	c.2819T>G	p.Ile940Ser	missense_variant	20/20		XP_011525164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK5	ENST00000593562.6	c.2816T>G	p.Ile939Ser	missense_variant	20/20	5	NM_002088.5	ENSP00000470251.1
GRIK5	ENST00000262895.7	c.2816T>G	p.Ile939Ser	missense_variant	19/19	1		ENSP00000262895.2
GRIK5	ENST00000454993.6	n.1693T>G		non_coding_transcript_exon_variant	9/9	1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.2816T>G (p.I939S) alteration is located in exon 19 (coding exon 19) of the GRIK5 gene. This alteration results from a T to G substitution at nucleotide position 2816, causing the isoleucine (I) at amino acid position 939 to be replaced by a serine (S). 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	0.83
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.079
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-0.63	N;.
REVEL	Benign	0.19
Sift	Uncertain	0.0060	D;.
Sift4G	Uncertain	0.013	D;D
Polyphen		0.28	B;B
Vest4		0.41
MutPred		0.25		Gain of phosphorylation at I939 (P = 0.0535);Gain of phosphorylation at I939 (P = 0.0535);
MVP		0.30
MPC		1.4
ClinPred		0.71	D
GERP RS		2.2
Varity_R		0.20

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.

Other links and lift over

hg19: chr19-42503150;