rs778828614

Variant names:

• chr10-85602550-C-A
• rs778828614
• NM_017551.3:c.2753G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-85602550-C-A
• chr10-85602550-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017551.3(GRID1):​c.2753G>T​(p.Arg918Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R918Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GRID1 NM_017551.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 2 publications found

Genes affected

GRID1 (HGNC:4575): (glutamate ionotropic receptor delta type subunit 1) This gene encodes a subunit of glutamate receptor channels. These channels mediate most of the fast excitatory synaptic transmission in the central nervous system and play key roles in synaptic plasticity.[provided by RefSeq, Jan 2009]

GRID1-AS1 (HGNC:44131): (GRID1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017551.3. 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
	GRID1	NM_017551.3	MANE Select	c.2753G>T	p.Arg918Leu	missense	Exon 16 of 16	NP_060021.1	Q9ULK0-1
	GRID1-AS1	NR_038986.1		n.282-2845C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRID1	ENST00000327946.12	TSL:2 MANE Select	c.2753G>T	p.Arg918Leu	missense	Exon 16 of 16	ENSP00000330148.7	Q9ULK0-1
	GRID1	ENST00000464741.2	TSL:1	n.*318G>T		non_coding_transcript_exon	Exon 15 of 15	ENSP00000433064.1	G3V186
	GRID1	ENST00000552278.2	TSL:1	n.230G>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251050 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.086	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		7.9
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.026	D
Sift4G	Benign	0.096	T
Polyphen		0.99	D
Vest4		0.52
MutPred		0.23		Loss of helix (P = 0.0093)
MVP		0.37
MPC		0.94
ClinPred		0.88	D
GERP RS		5.7
Varity_R		0.25
gMVP		0.55
Mutation Taster		=25/75	disease causing

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: rs778828614; hg19: chr10-87362307;