chr9-76055477-G-A

Variant summary

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

The NM_001372043.1(PCSK5):​c.633-12478G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 151,254 control chromosomes in the GnomAD database, including 3,967 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 0.20 ( 3967 hom., cov: 32)

Consequence

PCSK5
NM_001372043.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.120
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=-0.96).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PCSK5NM_001372043.1 linkuse as main transcriptc.633-12478G>A intron_variant ENST00000674117.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PCSK5ENST00000674117.1 linkuse as main transcriptc.633-12478G>A intron_variant NM_001372043.1 A2
PCSK5ENST00000376752.9 linkuse as main transcriptc.633-12478G>A intron_variant 1 Q92824-2
PCSK5ENST00000545128.5 linkuse as main transcriptc.633-12478G>A intron_variant 5 P4Q92824-1
PCSK5ENST00000376767.7 linkuse as main transcriptn.1145-12478G>A intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.202
AC:
30472
AN:
151140
Hom.:
3966
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0541
Gnomad AMI
AF:
0.289
Gnomad AMR
AF:
0.199
Gnomad ASJ
AF:
0.291
Gnomad EAS
AF:
0.00175
Gnomad SAS
AF:
0.147
Gnomad FIN
AF:
0.317
Gnomad MID
AF:
0.353
Gnomad NFE
AF:
0.286
Gnomad OTH
AF:
0.219
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.202
AC:
30480
AN:
151254
Hom.:
3967
Cov.:
32
AF XY:
0.203
AC XY:
14968
AN XY:
73828
show subpopulations
Gnomad4 AFR
AF:
0.0540
Gnomad4 AMR
AF:
0.199
Gnomad4 ASJ
AF:
0.291
Gnomad4 EAS
AF:
0.00175
Gnomad4 SAS
AF:
0.148
Gnomad4 FIN
AF:
0.317
Gnomad4 NFE
AF:
0.286
Gnomad4 OTH
AF:
0.221
Alfa
AF:
0.267
Hom.:
3390
Bravo
AF:
0.186
Asia WGS
AF:
0.0620
AC:
218
AN:
3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.96
CADD
Benign
9.0
DANN
Benign
0.66

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: rs1258095; hg19: chr9-78670393; COSMIC: COSV65092567; API