10-85602638-C-T

Variant names:

• chr10-85602638-C-T
• NM_017551.3:c.2665G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017551.3(GRID1):​c.2665G>A​(p.Ala889Thr) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A889V) has been classified 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: 7.91

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20477226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRID1	NM_017551.3	c.2665G>A	p.Ala889Thr	missense_variant	Exon 16 of 16	ENST00000327946.12	NP_060021.1
GRID1	XM_047425122.1	c.1378G>A	p.Ala460Thr	missense_variant	Exon 9 of 9		XP_047281078.1
GRID1	XM_047425123.1	c.1378G>A	p.Ala460Thr	missense_variant	Exon 9 of 9		XP_047281079.1
GRID1-AS1	NR_038986.1	n.282-2757C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRID1	ENST00000327946.12	c.2665G>A	p.Ala889Thr	missense_variant	Exon 16 of 16	2	NM_017551.3	ENSP00000330148.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2665G>A (p.A889T) alteration is located in exon 16 (coding exon 16) of the GRID1 gene. This alteration results from a G to A substitution at nucleotide position 2665, causing the alanine (A) at amino acid position 889 to be replaced by a threonine (T). 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	0.090
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.066	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.97	L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.23
Sift	Benign	0.071	T
Sift4G	Benign	0.12	T
Polyphen		0.73	P
Vest4		0.36
MutPred		0.14		Gain of phosphorylation at A889 (P = 0.0333);
MVP		0.20
MPC		0.61
ClinPred		0.94	D
GERP RS		5.7
Varity_R		0.23
gMVP		0.49

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: chr10-87362395;