rs6691840

Variant names:

• chr1-36859876-A-C
• rs6691840
• NM_000831.4:c.928T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-36859876-A-C
• chr1-36859876-A-G
• chr1-36859876-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000831.4(GRIK3):​c.928T>G​(p.Ser310Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,613,172 control chromosomes in the GnomAD database, including 65,928 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.34 (10444 hom., cov: 32)
  • Exomes 𝑓: 0.27 (55484 hom.)
• Consequence: GRIK3 NM_000831.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.959
• Publications: 49 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.8945822E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000831.4. 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
	GRIK3	NM_000831.4	MANE Select	c.928T>G	p.Ser310Ala	missense	Exon 6 of 16	NP_000822.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK3	ENST00000373091.8	TSL:1 MANE Select	c.928T>G	p.Ser310Ala	missense	Exon 6 of 16	ENSP00000362183.3	Q13003-1
	GRIK3	ENST00000373093.4	TSL:1	c.928T>G	p.Ser310Ala	missense	Exon 6 of 15	ENSP00000362185.4	Q13003-2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52124 AN: 151968 Hom.: 10407 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.0497

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.327

GnomAD2 exomes AF: 0.268 AC: 67378 AN: 251074 AF XY: 0.263

Gnomad AFR exome AF: 0.565

Gnomad AMR exome AF: 0.252

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.0444

Gnomad FIN exome AF: 0.302

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.285

GnomAD4 exome AF: 0.266 AC: 389359 AN: 1461086 Hom.: 55484 Cov.: 33 AF XY: 0.265 AC XY: 192682 AN XY: 726882

African (AFR) AF: 0.573 AC: 19173 AN: 33434

American (AMR) AF: 0.257 AC: 11489 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 9087 AN: 26124

East Asian (EAS) AF: 0.0268 AC: 1065 AN: 39698

South Asian (SAS) AF: 0.222 AC: 19126 AN: 86236

European-Finnish (FIN) AF: 0.295 AC: 15740 AN: 53406

Middle Eastern (MID) AF: 0.287 AC: 1641 AN: 5726

European-Non Finnish (NFE) AF: 0.266 AC: 295432 AN: 1111404

Other (OTH) AF: 0.275 AC: 16606 AN: 60356

GnomAD4 genome AF: 0.343 AC: 52220 AN: 152086 Hom.: 10444 Cov.: 32 AF XY: 0.338 AC XY: 25127 AN XY: 74340

African (AFR) AF: 0.559 AC: 23187 AN: 41466

American (AMR) AF: 0.282 AC: 4322 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1157 AN: 3472

East Asian (EAS) AF: 0.0496 AC: 256 AN: 5162

South Asian (SAS) AF: 0.219 AC: 1057 AN: 4816

European-Finnish (FIN) AF: 0.298 AC: 3154 AN: 10590

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.267 AC: 18120 AN: 67960

Other (OTH) AF: 0.325 AC: 688 AN: 2114

Alfa AF: 0.290 Hom.: 8084

Bravo AF: 0.355

TwinsUK AF: 0.260 AC: 965

ALSPAC AF: 0.254 AC: 980

ESP6500AA AF: 0.538 AC: 2371

ESP6500EA AF: 0.267 AC: 2295

ExAC AF: 0.272 AC: 32979

EpiCase AF: 0.273

EpiControl AF: 0.273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	16
DANN	Benign	0.67
DEOGEN2	Benign	0.089	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.000029	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.5	N
PhyloP100		0.96
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.023
Sift	Benign	0.54	T
Sift4G	Benign	0.79	T
Polyphen		0.0	B
Vest4		0.057
MPC		0.54
ClinPred		0.0011	T
GERP RS		3.9
Varity_R		0.048
gMVP		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6691840; hg19: chr1-37325477; COSMIC: COSV66140566; COSMIC: COSV66140566;