chr12-121166114-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_002562.6(P2RX7):c.671C>T(p.Pro224Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. P224A) has been classified as Uncertain significance.
Frequency
Consequence
NM_002562.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
P2RX7 | NM_002562.6 | c.671C>T | p.Pro224Leu | missense_variant | 7/13 | ENST00000328963.10 | |
LOC105370032 | XR_001749352.3 | n.327+37384G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
P2RX7 | ENST00000328963.10 | c.671C>T | p.Pro224Leu | missense_variant | 7/13 | 1 | NM_002562.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250356Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135398
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461562Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727102
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 2021 | The c.671C>T (p.P224L) alteration is located in exon 7 (coding exon 7) of the P2RX7 gene. This alteration results from a C to T substitution at nucleotide position 671, causing the proline (P) at amino acid position 224 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at