chr12-112419122-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM2PM5PP2BP4
The NM_002834.5(PTPN11):c.11G>A(p.Arg4Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000729 in 1,371,288 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4G) has been classified as Likely pathogenic.
Frequency
Consequence
NM_002834.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTPN11 | NM_002834.5 | c.11G>A | p.Arg4Gln | missense_variant | 1/16 | ENST00000351677.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTPN11 | ENST00000351677.7 | c.11G>A | p.Arg4Gln | missense_variant | 1/16 | 1 | NM_002834.5 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 7.29e-7 AC: 1AN: 1371288Hom.: 0 Cov.: 30 AF XY: 0.00000148 AC XY: 1AN XY: 676608
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
RASopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 13, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects PTPN11 function (PMID: 32112654). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PTPN11 protein function. This variant has not been reported in the literature in individuals affected with PTPN11-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 4 of the PTPN11 protein (p.Arg4Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.