rs535416574
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PM1PM2BP4_StrongBS1_Supporting
The NM_002838.5(PTPRC):c.700A>G(p.Asn234Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000584 in 1,609,848 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N234S) has been classified as Uncertain significance.
Frequency
Consequence
NM_002838.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTPRC | NM_002838.5 | c.700A>G | p.Asn234Asp | missense_variant | 9/33 | ENST00000442510.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTPRC | ENST00000442510.8 | c.700A>G | p.Asn234Asp | missense_variant | 9/33 | 1 | NM_002838.5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152236Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000799 AC: 20AN: 250202Hom.: 0 AF XY: 0.0000812 AC XY: 11AN XY: 135484
GnomAD4 exome AF: 0.0000604 AC: 88AN: 1457494Hom.: 0 Cov.: 31 AF XY: 0.0000565 AC XY: 41AN XY: 725270
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152354Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74502
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 18, 2021 | The c.694A>G (p.N232D) alteration is located in exon 9 (coding exon 8) of the PTPRC gene. This alteration results from a A to G substitution at nucleotide position 694, causing the asparagine (N) at amino acid position 232 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Immunodeficiency 105 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 16, 2021 | - - |
Immunodeficiency 104 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 05, 2022 | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 234 of the PTPRC protein (p.Asn234Asp). This variant is present in population databases (rs535416574, 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: 577072). 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 aspartic 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at