chr19-1481916-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_017573.5(PCSK4):c.2111G>A(p.Arg704His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000326 in 1,594,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. R704C) has been classified as Likely benign.
Frequency
Consequence
NM_017573.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCSK4 | NM_017573.5 | c.2111G>A | p.Arg704His | missense_variant | 15/15 | ENST00000300954.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCSK4 | ENST00000300954.10 | c.2111G>A | p.Arg704His | missense_variant | 15/15 | 1 | NM_017573.5 | P1 | |
PCSK4 | ENST00000441747.6 | n.2153G>A | non_coding_transcript_exon_variant | 12/12 | 2 | ||||
PCSK4 | ENST00000586616.5 | n.2367G>A | non_coding_transcript_exon_variant | 10/10 | 2 | ||||
PCSK4 | ENST00000591201.5 | c.*915G>A | 3_prime_UTR_variant, NMD_transcript_variant | 14/14 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000191 AC: 29AN: 151808Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000310 AC: 7AN: 226082Hom.: 0 AF XY: 0.0000243 AC XY: 3AN XY: 123348
GnomAD4 exome AF: 0.0000159 AC: 23AN: 1442382Hom.: 0 Cov.: 33 AF XY: 0.0000154 AC XY: 11AN XY: 715316
GnomAD4 genome AF: 0.000191 AC: 29AN: 151808Hom.: 0 Cov.: 33 AF XY: 0.000162 AC XY: 12AN XY: 74114
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2023 | The c.2111G>A (p.R704H) alteration is located in exon 15 (coding exon 15) of the PCSK4 gene. This alteration results from a G to A substitution at nucleotide position 2111, causing the arginine (R) at amino acid position 704 to be replaced by a histidine (H). 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