10-85602587-C-T

Variant names:

• chr10-85602587-C-T
• NM_017551.3:c.2716G>A

Variant summary

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

The NM_017551.3(GRID1):​c.2716G>A​(p.Gly906Arg) variant causes a missense change. 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: GRID1 NM_017551.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28029048).

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.2716G>A	p.Gly906Arg	missense	Exon 16 of 16	NP_060021.1	Q9ULK0-1
	GRID1-AS1	NR_038986.1		n.282-2808C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRID1	ENST00000327946.12	TSL:2 MANE Select	c.2716G>A	p.Gly906Arg	missense	Exon 16 of 16	ENSP00000330148.7	Q9ULK0-1
	GRID1	ENST00000464741.2	TSL:1	n.*281G>A		non_coding_transcript_exon	Exon 15 of 15	ENSP00000433064.1	G3V186
	GRID1	ENST00000552278.2	TSL:1	n.193G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	Uncertain	0.37
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.97	L
PhyloP100		5.0
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.15
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.022	D
Polyphen		0.84	P
Vest4		0.50
MutPred		0.17		Gain of solvent accessibility (P = 0.0097)
MVP		0.12
MPC		0.88
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.36
gMVP		0.55
Mutation Taster		=75/25	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

hg19: chr10-87362344; COSMIC: COSV105243628;