chr9-137139640-C-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4BP6

The NM_007327.4(GRIN1):c.154C>G(p.Arg52Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R52Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

GRIN1
NM_007327.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.917

Publications

0 publications found

Variant links:

Genes affected

GRIN1 (HGNC:4584): (glutamate ionotropic receptor NMDA type subunit 1) The protein encoded by this gene is a critical subunit of N-methyl-D-aspartate receptors, members of the glutamate receptor channel superfamily which are heteromeric protein complexes with multiple subunits arranged to form a ligand-gated ion channel. These subunits play a key role in the plasticity of synapses, which is believed to underlie memory and learning. Cell-specific factors are thought to control expression of different isoforms, possibly contributing to the functional diversity of the subunits. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2008]

GRIN1 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
complex neurodevelopmental disorder
Inheritance: AR, AD Classification: DEFINITIVE Submitted by: ClinGen
neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, MODERATE Submitted by: G2P, Ambry Genetics
developmental and epileptic encephalopathy 101
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GRIN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.36100566).

BP6

Variant 9-137139640-C-G is Benign according to our data. Variant chr9-137139640-C-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 539838. Variant chr9-137139640-C-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 539838. Variant chr9-137139640-C-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 539838. Variant chr9-137139640-C-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 539838. Variant chr9-137139640-C-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 539838. Variant chr9-137139640-C-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 539838. Variant chr9-137139640-C-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 539838. Variant chr9-137139640-C-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 539838. Variant chr9-137139640-C-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 539838. Variant chr9-137139640-C-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 539838. Variant chr9-137139640-C-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 539838. Variant chr9-137139640-C-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 539838. Variant chr9-137139640-C-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 539838. Variant chr9-137139640-C-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 539838.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN1	NM_007327.4 link	c.154C>G	p.Arg52Gly	missense_variant	Exon 1 of 20	ENST00000371561.8	NP_015566.1	Q05586-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN1	ENST00000371561.8 link	c.154C>G	p.Arg52Gly	missense_variant	Exon 1 of 20	1	NM_007327.4	ENSP00000360616.3		Q05586-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000800

AC:

AN:

250114

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461466

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727040

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.0000671

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53168

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111846

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Mar 25, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.154C>G (p.R52G) alteration is located in exon 1 (coding exon 1) of the GRIN1 gene. This alteration results from a C to G substitution at nucleotide position 154, causing the arginine (R) at amino acid position 52 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant

Benign:1

Jun 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

T;.;.;T;.;.;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.12

LIST_S2

Uncertain

0.96

D;D;D;D;D;D;D

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.36

T;T;T;T;T;T;T

MetaSVM

Benign

-0.36

MutationAssessor

Benign

0.34

N;N;N;.;N;N;N

PhyloP100

0.92

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.0

N;N;N;N;N;N;N

REVEL

Benign

0.26

Sift

Benign

0.070

T;T;T;T;T;T;T

Sift4G

Benign

0.37

T;T;T;T;T;T;T

Polyphen

0.47

P;P;.;.;.;B;.

Vest4

0.38

MutPred

0.36

Loss of stability (P = 0.0211);Loss of stability (P = 0.0211);Loss of stability (P = 0.0211);Loss of stability (P = 0.0211);Loss of stability (P = 0.0211);Loss of stability (P = 0.0211);Loss of stability (P = 0.0211);

MVP

0.87

MPC

2.3

ClinPred

0.34

GERP RS

2.2

PromoterAI

-0.026

Neutral

(source)

Varity_R

0.34

gMVP

0.82

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over