10-85613478-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017551.3(GRID1):c.2530C>G(p.Leu844Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.75

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRID1	NM_017551.3	c.2530C>G	p.Leu844Val	missense_variant	15/16	ENST00000327946.12
GRID1	XM_047425122.1	c.1243C>G	p.Leu415Val	missense_variant	8/9
GRID1	XM_047425123.1	c.1243C>G	p.Leu415Val	missense_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRID1	ENST00000327946.12	c.2530C>G	p.Leu844Val	missense_variant	15/16	2	NM_017551.3	P1
GRID1	ENST00000464741.2	c.*95C>G		3_prime_UTR_variant, NMD_transcript_variant	14/15	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2023

The c.2530C>G (p.L844V) alteration is located in exon 15 (coding exon 15) of the GRID1 gene. This alteration results from a C to G substitution at nucleotide position 2530, causing the leucine (L) at amino acid position 844 to be replaced by a valine (V). 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	0.13
BayesDel_addAF	Benign	-0.0044	T
BayesDel_noAF	Benign	-0.24
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.25
Sift	Benign	0.15	T
Sift4G	Uncertain	0.027	D
Polyphen		0.99	D
Vest4		0.68
MutPred		0.72		Gain of catalytic residue at L844 (P = 0.0075);
MVP		0.31
MPC		0.84
ClinPred		0.94	D
GERP RS		5.4
Varity_R		0.26
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-87373235; COSMIC: COSV100024282; COSMIC: COSV100024282;