rs1353342

Variant names:

• chr9-76259853-A-C
• rs1353342
• NM_001372043.1:c.3142+19169A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-76259853-A-C
• chr9-76259853-A-G
• chr9-76259853-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372043.1(PCSK5):​c.3142+19169A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 151,936 control chromosomes in the GnomAD database, including 49,172 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 0.79 (49172 hom., cov: 29)
• Consequence: PCSK5 NM_001372043.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376
• Publications: 4 publications found

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]

PCSK5 Gene-Disease associations (from GenCC):

• syndromic congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372043.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCSK5	NM_001372043.1	MANE Select	c.3142+19169A>C		intron	N/A	NP_001358972.1	A0A669KA35
	PCSK5	NM_001190482.2		c.3142+19169A>C		intron	N/A	NP_001177411.1	Q92824-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCSK5	ENST00000674117.1	MANE Select	c.3142+19169A>C		intron	N/A	ENSP00000500971.1	A0A669KA35
	PCSK5	ENST00000854198.1		c.3142+19169A>C		intron	N/A	ENSP00000524257.1
	PCSK5	ENST00000545128.5	TSL:5	c.3142+19169A>C		intron	N/A	ENSP00000446280.1	Q92824-1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120230 AN: 151818 Hom.: 49141 Cov.: 29

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.823

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.792 AC: 120310 AN: 151936 Hom.: 49172 Cov.: 29 AF XY: 0.794 AC XY: 58992 AN XY: 74282

African (AFR) AF: 0.559 AC: 23154 AN: 41438

American (AMR) AF: 0.855 AC: 13051 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3042 AN: 3468

East Asian (EAS) AF: 0.910 AC: 4652 AN: 5110

South Asian (SAS) AF: 0.828 AC: 3981 AN: 4810

European-Finnish (FIN) AF: 0.882 AC: 9318 AN: 10560

Middle Eastern (MID) AF: 0.757 AC: 221 AN: 292

European-Non Finnish (NFE) AF: 0.887 AC: 60313 AN: 67972

Other (OTH) AF: 0.823 AC: 1735 AN: 2108

Alfa AF: 0.860 Hom.: 109681

Bravo AF: 0.781

Asia WGS AF: 0.853 AC: 2965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.65
DANN	Benign	0.49
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1353342; hg19: chr9-78874769;