NM_014619.5:c.386T>C

Variant names:

• chr11-120819795-T-C
• rs1008330546
• NM_014619.5:c.386T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014619.5(GRIK4):​c.386T>C​(p.Phe129Ser) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 32)
• Consequence: GRIK4 NM_014619.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.63
• Publications: 0 publications found

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]

ENSG00000306735 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30054128).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014619.5. 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
	GRIK4	NM_014619.5	MANE Select	c.386T>C	p.Phe129Ser	missense	Exon 6 of 21	NP_055434.2
	GRIK4	NM_001282470.3		c.386T>C	p.Phe129Ser	missense	Exon 5 of 20	NP_001269399.1	A0A8D9PH79
	GRIK4	NM_001440402.1		c.386T>C	p.Phe129Ser	missense	Exon 8 of 23	NP_001427331.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK4	ENST00000527524.8	TSL:2 MANE Select	c.386T>C	p.Phe129Ser	missense	Exon 6 of 21	ENSP00000435648.2	Q16099
	GRIK4	ENST00000438375.2	TSL:1	c.386T>C	p.Phe129Ser	missense	Exon 5 of 20	ENSP00000404063.2	Q16099
	GRIK4	ENST00000533291.5	TSL:1	n.784T>C		non_coding_transcript_exon	Exon 6 of 18

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.087
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.6
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.78	N
REVEL	Uncertain	0.38
Sift	Benign	0.40	T
Sift4G	Benign	0.40	T
Polyphen		0.40	B
Vest4		0.45
MutPred		0.42		Gain of disorder (P = 0.0242)
MVP		0.73
MPC		0.99
ClinPred		0.85	D
GERP RS		4.3
Varity_R		0.21
gMVP		0.70
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs1008330546; hg19: chr11-120690504;