Variant 10-85613411-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017551.3(GRID1):c.2597A>G(p.Lys866Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,272 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GRID1
NM_017551.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34508967).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GRID1	NM_017551.3 linkuse as main transcript	c.2597A>G	p.Lys866Arg	missense_variant	15/16	ENST00000327946.12	NP_060021.1
GRID1	XM_047425122.1 linkuse as main transcript	c.1310A>G	p.Lys437Arg	missense_variant	8/9		XP_047281078.1
GRID1	XM_047425123.1 linkuse as main transcript	c.1310A>G	p.Lys437Arg	missense_variant	8/9		XP_047281079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRID1	ENST00000327946.12 linkuse as main transcript	c.2597A>G	p.Lys866Arg	missense_variant	15/16	2	NM_017551.3	ENSP00000330148	P1	Q9ULK0-1
GRID1	ENST00000464741.2 linkuse as main transcript	c.*162A>G		3_prime_UTR_variant, NMD_transcript_variant	14/15	1		ENSP00000433064

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460272

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726354

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2022

The c.2597A>G (p.K866R) alteration is located in exon 15 (coding exon 15) of the GRID1 gene. This alteration results from a A to G substitution at nucleotide position 2597, causing the lysine (K) at amino acid position 866 to be replaced by an arginine (R). 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

0.11

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

Eigen

Benign

0.088

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.012

MetaRNN

Benign

0.35

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.71

REVEL

Benign

0.077

Sift

Benign

0.40

Sift4G

Benign

0.18

Polyphen

0.14

Vest4

0.65

MutPred

0.29

Loss of ubiquitination at K866 (P = 0.0047);

MVP

0.42

MPC

0.60

ClinPred

0.91

GERP RS

5.4

Varity_R

0.10

gMVP

0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over