chr1-36859876-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000831.4(GRIK3):​c.928T>A​(p.Ser310Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,634 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S310A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: GRIK3 NM_000831.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.959

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050253093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK3	NM_000831.4	c.928T>A	p.Ser310Thr	missense_variant	Exon 6 of 16	ENST00000373091.8	NP_000822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK3	ENST00000373091.8	c.928T>A	p.Ser310Thr	missense_variant	Exon 6 of 16	1	NM_000831.4	ENSP00000362183.3
GRIK3	ENST00000373093.4	c.928T>A	p.Ser310Thr	missense_variant	Exon 6 of 15	1		ENSP00000362185.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461634 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727106

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	17
DANN	Benign	0.72
DEOGEN2	Benign	0.085	T;.
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.26	N;N
REVEL	Benign	0.021
Sift	Benign	0.24	T;T
Sift4G	Benign	0.60	T;T
Polyphen		0.0	B;.
Vest4		0.11
MutPred		0.41		Loss of disorder (P = 0.0679);Loss of disorder (P = 0.0679);
MVP		0.19
MPC		0.60
ClinPred		0.084	T
GERP RS		3.9
Varity_R		0.049
gMVP		0.45

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

LitVar

Other links and lift over

dbSNP: rs6691840; hg19: chr1-37325477; COSMIC: COSV66135305; COSMIC: COSV66135305;