chr12-13563245-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_000834.5(GRIN2B):c.3993G>A(p.Met1331Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,614,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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. M1331L) has been classified as Benign.
Frequency
Consequence
NM_000834.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIN2B | NM_000834.5 | c.3993G>A | p.Met1331Ile | missense_variant | 14/14 | ENST00000609686.4 | |
GRIN2B | NM_001413992.1 | c.3993G>A | p.Met1331Ile | missense_variant | 15/15 | ||
GRIN2B | XM_005253351.3 | c.1779G>A | p.Met593Ile | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIN2B | ENST00000609686.4 | c.3993G>A | p.Met1331Ile | missense_variant | 14/14 | 1 | NM_000834.5 | P1 | |
GRIN2B | ENST00000637214.1 | c.69+45358G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251396Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135884
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461894Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 12AN XY: 727248
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152346Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74502
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Feb 06, 2017 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 25, 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 31, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Intellectual disability, autosomal dominant 6;C4015316:Developmental and epileptic encephalopathy, 27 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 21, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at