10-85647345-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017551.3(GRID1):c.2050G>C(p.Asp684His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GRID1 NM_017551.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.817

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRID1	NM_017551.3	c.2050G>C	p.Asp684His	missense_variant	13/16	ENST00000327946.12
GRID1	XM_047425122.1	c.763G>C	p.Asp255His	missense_variant	6/9
GRID1	XM_047425123.1	c.763G>C	p.Asp255His	missense_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRID1	ENST00000327946.12	c.2050G>C	p.Asp684His	missense_variant	13/16	2	NM_017551.3	P1
	ENST00000474115.2	n.1898C>G		non_coding_transcript_exon_variant	2/2	2
GRID1	ENST00000464741.2	c.2050G>C	p.Asp684His	missense_variant, NMD_transcript_variant	13/15	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

GRID1-associated neurodevelopmental disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Institute of Human Genetics, University of Leipzig Medical Center

May 08, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.0029	T
BayesDel_noAF	Benign	-0.24
Cadd	Pathogenic	28
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.84	P
Vest4		0.77
MutPred		0.80		Loss of sheet (P = 0.0817);
MVP		0.22
MPC		0.84
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.72
gMVP		0.86

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: chr10-87407102;