19-41999254-A-T

Position:

• chr19-41999254-A-T

Variant summary

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

The NM_002088.5(GRIK5):​c.2560T>A​(p.Ser854Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S854C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GRIK5 NM_002088.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06

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]

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=0.14767629).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK5	NM_002088.5	c.2560T>A	p.Ser854Thr	missense_variant	20/20	ENST00000593562.6
GRIK5	XM_011526862.3	c.2563T>A	p.Ser855Thr	missense_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK5	ENST00000593562.6	c.2560T>A	p.Ser854Thr	missense_variant	20/20	5	NM_002088.5	P1
GRIK5	ENST00000262895.7	c.2560T>A	p.Ser854Thr	missense_variant	19/19	1		P1
GRIK5	ENST00000454993.6	n.1437T>A		non_coding_transcript_exon_variant	9/9	1
GRIK5	ENST00000602210.1	n.378T>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Uncertain	24
DANN	Benign	0.93
DEOGEN2	Benign	0.065	T;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.79	D
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L;L
MutationTaster	Benign	0.91	D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.26	N;.
REVEL	Benign	0.026
Sift	Benign	0.65	T;.
Sift4G	Benign	0.61	T;T
Polyphen		0.37	B;B
Vest4		0.26
MutPred		0.24		Gain of glycosylation at S854 (P = 0.1116);Gain of glycosylation at S854 (P = 0.1116);
MVP		0.60
MPC		0.90
ClinPred		0.24	T
GERP RS		2.6
Varity_R		0.085

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: chr19-42503406;