rs767000671
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_007327.4(GRIN1):c.152A>G(p.Lys51Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,752 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
GRIN1
NM_007327.4 missense
NM_007327.4 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 4.99
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, GRIN1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.14217842).
BP6
?
Variant 9-137139638-A-G is Benign according to our data. Variant chr9-137139638-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 472572.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIN1 | NM_007327.4 | c.152A>G | p.Lys51Arg | missense_variant | 1/20 | ENST00000371561.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIN1 | ENST00000371561.8 | c.152A>G | p.Lys51Arg | missense_variant | 1/20 | 1 | NM_007327.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152150Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000320 AC: 8AN: 250244Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135452
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461602Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727096
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74322
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2019 | The p.K51R variant (also known as c.152A>G), located in coding exon 1 of the GRIN1 gene, results from an A to G substitution at nucleotide position 152. The lysine at codon 51 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 27, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Intellectual disability, autosomal dominant 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 16, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;.;T;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;.;N;N;N
MutationTaster
Benign
N;N;N;N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
B;B;.;.;.;B;.
Vest4
MutPred
Loss of ubiquitination at K51 (P = 0.0412);Loss of ubiquitination at K51 (P = 0.0412);Loss of ubiquitination at K51 (P = 0.0412);Loss of ubiquitination at K51 (P = 0.0412);Loss of ubiquitination at K51 (P = 0.0412);Loss of ubiquitination at K51 (P = 0.0412);Loss of ubiquitination at K51 (P = 0.0412);
MVP
MPC
1.1
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at