rs149798940
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_002838.5(PTPRC):c.260C>T(p.Pro87Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,614,088 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P87P) has been classified as Likely benign.
Frequency
Consequence
NM_002838.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTPRC | NM_002838.5 | c.260C>T | p.Pro87Leu | missense_variant | 4/33 | ENST00000442510.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTPRC | ENST00000442510.8 | c.260C>T | p.Pro87Leu | missense_variant | 4/33 | 1 | NM_002838.5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000322 AC: 49AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000119 AC: 30AN: 251476Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135912
GnomAD4 exome AF: 0.0000821 AC: 120AN: 1461808Hom.: 1 Cov.: 32 AF XY: 0.0000880 AC XY: 64AN XY: 727220
GnomAD4 genome ? AF: 0.000322 AC: 49AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.000416 AC XY: 31AN XY: 74468
ClinVar
Submissions by phenotype
Immunodeficiency 104 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 13, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 87 of the PTPRC protein (p.Pro87Leu). This variant is present in population databases (rs149798940, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with PTPRC-related conditions. ClinVar contains an entry for this variant (Variation ID: 573532). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 17, 2023 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at