rs508487
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_004716.4(PCSK7):c.*1147G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 267,740 control chromosomes in the GnomAD database, including 718 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.055 ( 321 hom., cov: 32)
Exomes 𝑓: 0.073 ( 397 hom. )
Consequence
PCSK7
NM_004716.4 3_prime_UTR
NM_004716.4 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.284
Genes affected
TAGLN (HGNC:11553): (transgelin) This gene encodes a shape change and transformation sensitive actin-binding protein which belongs to the calponin family. It is ubiquitously expressed in vascular and visceral smooth muscle, and is an early marker of smooth muscle differentiation. The encoded protein is thought to be involved in calcium-independent smooth muscle contraction. It acts as a tumor suppressor, and the loss of its expression is an early event in cell transformation and the development of some tumors, coinciding with cellular plasticity. The encoded protein has a domain architecture consisting of an N-terminal calponin homology (CH) domain and a C-terminal calponin-like (CLIK) domain. Mice with a knockout of the orthologous gene are viable and fertile but their vascular smooth muscle cells exhibit alterations in the distribution of the actin filament and changes in cytoskeletal organization. [provided by RefSeq, Aug 2017]
PCSK7 (HGNC:8748): (proprotein convertase subtilisin/kexin type 7) This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. It encodes a type 1 membrane bound protease that is expressed in many tissues, including neuroendocrine, liver, gut, and brain. The encoded protein undergoes an initial autocatalytic processing event in the ER and then sorts to the trans-Golgi network through endosomes where a second autocatalytic event takes place and the catalytic activity is acquired. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It can process proalbumin and is thought to be responsible for the activation of HIV envelope glycoproteins gp160 and gp140. This gene has been implicated in the transcriptional regulation of housekeeping genes and plays a role in the regulation of iron metabolism. A t(11;14)(q23;q32) chromosome translocation associated with B-cell lymphoma occurs between this gene and its inverted counterpart. [provided by RefSeq, Feb 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAGLN | NM_003186.5 | c.*491C>T | 3_prime_UTR_variant | 5/5 | ENST00000392951.9 | ||
PCSK7 | NM_004716.4 | c.*1147G>A | 3_prime_UTR_variant | 17/17 | ENST00000320934.8 | ||
TAGLN | NM_001001522.2 | c.*491C>T | 3_prime_UTR_variant | 5/5 | |||
PCSK7 | XM_006718940.5 | c.*1147G>A | 3_prime_UTR_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCSK7 | ENST00000320934.8 | c.*1147G>A | 3_prime_UTR_variant | 17/17 | 1 | NM_004716.4 | P1 | ||
TAGLN | ENST00000392951.9 | c.*491C>T | 3_prime_UTR_variant | 5/5 | 1 | NM_003186.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0547 AC: 8305AN: 151830Hom.: 318 Cov.: 32
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GnomAD4 exome AF: 0.0728 AC: 8432AN: 115814Hom.: 397 Cov.: 0 AF XY: 0.0762 AC XY: 4508AN XY: 59154
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GnomAD4 genome ? AF: 0.0547 AC: 8311AN: 151926Hom.: 321 Cov.: 32 AF XY: 0.0566 AC XY: 4200AN XY: 74220
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at