rs1176211628
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_018026.4(PACS1):c.101_103dup(p.Pro34dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,491,794 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
PACS1
NM_018026.4 inframe_insertion
NM_018026.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.25
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 Likely_benign. Variant got -5 ACMG points.
BP6
?
Variant 11-66070578-A-AGCC is Benign according to our data. Variant chr11-66070578-A-AGCC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211810.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS2
?
High AC in GnomAdExome4 at 24 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PACS1 | NM_018026.4 | c.101_103dup | p.Pro34dup | inframe_insertion | 1/24 | ENST00000320580.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PACS1 | ENST00000320580.9 | c.101_103dup | p.Pro34dup | inframe_insertion | 1/24 | 1 | NM_018026.4 | P2 | |
PACS1 | ENST00000527224.1 | n.225_227dup | non_coding_transcript_exon_variant | 1/7 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000660 AC: 1AN: 151404Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000128 AC: 12AN: 93462Hom.: 0 AF XY: 0.0000753 AC XY: 4AN XY: 53146
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GnomAD4 exome AF: 0.0000179 AC: 24AN: 1340390Hom.: 0 Cov.: 31 AF XY: 0.0000242 AC XY: 16AN XY: 661462
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GnomAD4 genome ? AF: 0.00000660 AC: 1AN: 151404Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 73918
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 20, 2014 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 04, 2018 | See Variant Classification Assertion Criteria. - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at