8-42176054-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000930.5(PLAT):c.1628C>T(p.Pro543Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,866 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 (★). Synonymous variant affecting the same amino acid position (i.e. P543P) has been classified as Likely benign.
Frequency
Consequence
NM_000930.5 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 |
---|---|---|---|---|---|---|---|
PLAT | NM_000930.5 | c.1628C>T | p.Pro543Leu | missense_variant | 14/14 | ENST00000220809.9 | |
PLAT | NM_033011.4 | c.1490C>T | p.Pro497Leu | missense_variant | 13/13 | ||
PLAT | NM_001319189.2 | c.1361C>T | p.Pro454Leu | missense_variant | 12/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLAT | ENST00000220809.9 | c.1628C>T | p.Pro543Leu | missense_variant | 14/14 | 1 | NM_000930.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152144Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251314Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135834
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461722Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727162
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152144Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74306
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 03, 2022 | The c.1628C>T (p.P543L) alteration is located in exon 14 (coding exon 13) of the PLAT gene. This alteration results from a C to T substitution at nucleotide position 1628, causing the proline (P) at amino acid position 543 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