chr11-66070573-TCAGCAGCCGCCGCCGCAGCAGCAGCAG-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018026.4(PACS1):c.101_127del(p.Pro34_Pro42del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000299 in 1,335,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000030 ( 0 hom. )
Consequence
PACS1
NM_018026.4 inframe_deletion
NM_018026.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.85
Genes affected
PACS1 (HGNC:30032): (phosphofurin acidic cluster sorting protein 1) This gene encodes a protein with a putative role in the localization of trans-Golgi network (TGN) membrane proteins. Mouse and rat homologs have been identified and studies of the homologous rat protein indicate a role in directing TGN localization of furin by binding to the protease's phosphorylated cytosolic domain. In addition, the human protein plays a role in HIV-1 Nef-mediated downregulation of cell surface MHC-I molecules to the TGN, thereby enabling HIV-1 to escape immune surveillance. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PACS1 | NM_018026.4 | c.101_127del | p.Pro34_Pro42del | inframe_deletion | 1/24 | ENST00000320580.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PACS1 | ENST00000320580.9 | c.101_127del | p.Pro34_Pro42del | inframe_deletion | 1/24 | 1 | NM_018026.4 | P2 | |
PACS1 | ENST00000527224.1 | n.225_251del | non_coding_transcript_exon_variant | 1/7 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000112 AC: 1AN: 89510Hom.: 0 AF XY: 0.0000197 AC XY: 1AN XY: 50754
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GnomAD4 exome AF: 0.00000299 AC: 4AN: 1335630Hom.: 0 AF XY: 0.00000455 AC XY: 3AN XY: 658800
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
PACS1-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 22, 2024 | The PACS1 c.101_127del27 variant is predicted to result in an in-frame deletion (p.Pro34_Pro42del). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0053% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at