rs61749266
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_002838.5(PTPRC):āc.1441A>Gā(p.Lys481Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,613,584 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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. K481R) has been classified as Uncertain significance.
Frequency
Consequence
NM_002838.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTPRC | NM_002838.5 | c.1441A>G | p.Lys481Glu | missense_variant | 13/33 | ENST00000442510.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTPRC | ENST00000442510.8 | c.1441A>G | p.Lys481Glu | missense_variant | 13/33 | 1 | NM_002838.5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000709 AC: 108AN: 152256Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000777 AC: 195AN: 251058Hom.: 0 AF XY: 0.000847 AC XY: 115AN XY: 135700
GnomAD4 exome AF: 0.00157 AC: 2300AN: 1461210Hom.: 5 Cov.: 31 AF XY: 0.00153 AC XY: 1114AN XY: 726918
GnomAD4 genome ? AF: 0.000709 AC: 108AN: 152374Hom.: 0 Cov.: 32 AF XY: 0.000564 AC XY: 42AN XY: 74516
ClinVar
Submissions by phenotype
Immunodeficiency 104 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 28, 2022 | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 481 of the PTPRC protein (p.Lys481Glu). This variant is present in population databases (rs61749266, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. 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: 575499). 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 glutamic acid 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 21, 2022 | 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