10-85647339-C-T

Variant names:

• chr10-85647339-C-T
• NM_017551.3:c.2056G>A

Variant summary

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

The NM_017551.3(GRID1):​c.2056G>A​(p.Ala686Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.50

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]

ENSG00000270002 (HGNC:):

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 rank	MANE	Protein	UniProt
GRID1	NM_017551.3	c.2056G>A	p.Ala686Thr	missense_variant	Exon 13 of 16	ENST00000327946.12	NP_060021.1
GRID1	XM_047425122.1	c.769G>A	p.Ala257Thr	missense_variant	Exon 6 of 9		XP_047281078.1
GRID1	XM_047425123.1	c.769G>A	p.Ala257Thr	missense_variant	Exon 6 of 9		XP_047281079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRID1	ENST00000327946.12	c.2056G>A	p.Ala686Thr	missense_variant	Exon 13 of 16	2	NM_017551.3	ENSP00000330148.7
GRID1	ENST00000464741.2	n.2056G>A		non_coding_transcript_exon_variant	Exon 13 of 15	1		ENSP00000433064.1
ENSG00000270002	ENST00000474115.2	n.1892C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

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

not specified Uncertain:1

Aug 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2056G>A (p.A686T) alteration is located in exon 13 (coding exon 13) of the GRID1 gene. This alteration results from a G to A substitution at nucleotide position 2056, causing the alanine (A) at amino acid position 686 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	0.25
BayesDel_addAF	Benign	0.0093	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.10	T
Polyphen		0.51	P
Vest4		0.85
MutPred		0.65		Gain of phosphorylation at A686 (P = 0.0438);
MVP		0.38
MPC		0.44
ClinPred		0.96	D
GERP RS		5.7
Varity_R		0.35
gMVP		0.74

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: chr10-87407096; COSMIC: COSV60057322; COSMIC: COSV60057322;