chr15-74033264-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_033238.3(PML):c.1507C>T(p.Arg503Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_033238.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PML | NM_033238.3 | c.1507C>T | p.Arg503Trp | missense_variant | 6/9 | ENST00000268058.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PML | ENST00000268058.8 | c.1507C>T | p.Arg503Trp | missense_variant | 6/9 | 1 | NM_033238.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251294Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135834
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727238
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152328Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74496
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 28, 2022 | The c.1507C>T (p.R503W) alteration is located in exon 6 (coding exon 6) of the PML gene. This alteration results from a C to T substitution at nucleotide position 1507, causing the arginine (R) at amino acid position 503 to be replaced by a tryptophan (W). 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