9-75890973-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001372043.1(PCSK5):​c.-209G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0945 in 410,616 control chromosomes in the GnomAD database, including 3,766 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 0.14 ( 2741 hom., cov: 33)
Exomes 𝑓: 0.068 ( 1025 hom. )

Consequence

PCSK5
NM_001372043.1 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.43
Variant links:
Genes affected
PCSK5 (HGNC:8747): (proprotein convertase subtilisin/kexin type 5) 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. The encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER. It then sorts to the trans-Golgi network where a second autocatalytic event takes place and the catalytic activity is acquired. This encoded protein is widely expressed and one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It mediates posttranslational endoproteolytic processing for several integrin alpha subunits and is thought to process prorenin, pro-membrane type-1 matrix metalloproteinase and HIV-1 glycoprotein gp160. Alternative splicing results in multiple transcript variants, some of which encode distinct isoforms, including a protease packaged into dense core granules (PC5A) and a type 1 membrane bound protease (PC5B). [provided by RefSeq, May 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=-0.8).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCSK5NM_001372043.1 linkc.-209G>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 38 ENST00000674117.1 NP_001358972.1
PCSK5NM_001372043.1 linkc.-209G>T 5_prime_UTR_variant Exon 1 of 38 ENST00000674117.1 NP_001358972.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCSK5ENST00000674117 linkc.-209G>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 38 NM_001372043.1 ENSP00000500971.1 A0A669KA35
PCSK5ENST00000674117 linkc.-209G>T 5_prime_UTR_variant Exon 1 of 38 NM_001372043.1 ENSP00000500971.1 A0A669KA35

Frequencies

GnomAD3 genomes
AF:
0.139
AC:
21177
AN:
152002
Hom.:
2737
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.339
Gnomad AMI
AF:
0.0548
Gnomad AMR
AF:
0.0736
Gnomad ASJ
AF:
0.0499
Gnomad EAS
AF:
0.000775
Gnomad SAS
AF:
0.0219
Gnomad FIN
AF:
0.0906
Gnomad MID
AF:
0.149
Gnomad NFE
AF:
0.0652
Gnomad OTH
AF:
0.119
GnomAD4 exome
AF:
0.0681
AC:
17607
AN:
258500
Hom.:
1025
Cov.:
4
AF XY:
0.0656
AC XY:
8657
AN XY:
132010
show subpopulations
Gnomad4 AFR exome
AF:
0.338
Gnomad4 AMR exome
AF:
0.0664
Gnomad4 ASJ exome
AF:
0.0527
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0267
Gnomad4 FIN exome
AF:
0.0856
Gnomad4 NFE exome
AF:
0.0640
Gnomad4 OTH exome
AF:
0.0871
GnomAD4 genome
AF:
0.139
AC:
21194
AN:
152116
Hom.:
2741
Cov.:
33
AF XY:
0.137
AC XY:
10208
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.339
Gnomad4 AMR
AF:
0.0734
Gnomad4 ASJ
AF:
0.0499
Gnomad4 EAS
AF:
0.000972
Gnomad4 SAS
AF:
0.0217
Gnomad4 FIN
AF:
0.0906
Gnomad4 NFE
AF:
0.0652
Gnomad4 OTH
AF:
0.118
Alfa
AF:
0.0484
Hom.:
58
Bravo
AF:
0.148
Asia WGS
AF:
0.0290
AC:
100
AN:
3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
5.7
DANN
Benign
0.84

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12005073; hg19: chr9-78505889; COSMIC: COSV65097178; API