19-1482112-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_017573.5(PCSK4):c.1915G>C(p.Gly639Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000573 in 1,552,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.
Frequency
Consequence
NM_017573.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCSK4 | NM_017573.5 | c.1915G>C | p.Gly639Arg | missense_variant | Exon 15 of 15 | ENST00000300954.10 | NP_060043.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000582 AC: 9AN: 154690Hom.: 0 AF XY: 0.0000706 AC XY: 6AN XY: 85030
GnomAD4 exome AF: 0.0000607 AC: 85AN: 1400746Hom.: 0 Cov.: 33 AF XY: 0.0000678 AC XY: 47AN XY: 692844
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74352
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1915G>C (p.G639R) alteration is located in exon 15 (coding exon 15) of the PCSK4 gene. This alteration results from a G to C substitution at nucleotide position 1915, causing the glycine (G) at amino acid position 639 to be replaced by an arginine (R). 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