rs200538196

Variant names:

• chr11-120660364-G-A
• rs200538196
• NM_014619.5:c.46G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-120660364-G-A
• chr11-120660364-G-C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014619.5(GRIK4):​c.46G>A​(p.Val16Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,613,292 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: GRIK4 NM_014619.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.395
• Publications: 3 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.041639537).
• BS2: High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK4	NM_014619.5	c.46G>A	p.Val16Met	missense_variant	Exon 3 of 21	ENST00000527524.8	NP_055434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK4	ENST00000527524.8	c.46G>A	p.Val16Met	missense_variant	Exon 3 of 21	2	NM_014619.5	ENSP00000435648.2

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000163 AC: 41 AN: 250776 AF XY: 0.000192

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000157 AC: 229 AN: 1460970 Hom.: 1 Cov.: 31 AF XY: 0.000146 AC XY: 106 AN XY: 726872

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.000224 AC: 10 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52582

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5766

European-Non Finnish (NFE) AF: 0.000179 AC: 199 AN: 1111952

Other (OTH) AF: 0.000166 AC: 10 AN: 60380

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152322 Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74490

African (AFR) AF: 0.0000240 AC: 1 AN: 41588

American (AMR) AF: 0.000196 AC: 3 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.000287 Hom.: 0

Bravo AF: 0.000162

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000157 AC: 19

EpiCase AF: 0.000872

EpiControl AF: 0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.46G>A (p.V16M) alteration is located in exon 1 (coding exon 1) of the GRIK4 gene. This alteration results from a G to A substitution at nucleotide position 46, causing the valine (V) at amino acid position 16 to be replaced by a methionine (M). 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	Benign	0.12
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.059	T;T;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.62	.;.;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.042	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;N
PhyloP100		0.40
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.46	N;.;N
REVEL	Benign	0.11
Sift	Benign	0.26	T;.;T
Sift4G	Benign	0.19	T;.;T
Polyphen		0.0040	B;B;B
Vest4		0.31
MVP		0.093
MPC		0.51
ClinPred		0.054	T
GERP RS		-4.3
Varity_R		0.037
gMVP		0.28
Mutation Taster		=100/0	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: rs200538196; hg19: chr11-120531073;