rs1331384

Variant names:

• chr9-76144372-G-A
• rs1331384
• NM_001372043.1:c.1312+10160G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-76144372-G-A
• chr9-76144372-G-C
• chr9-76144372-G-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.1312+10160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 152,016 control chromosomes in the GnomAD database, including 25,221 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 0.57 (25221 hom., cov: 33)
• Consequence: PCSK5 NM_001372043.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 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.1312+10160G>A		intron	N/A	NP_001358972.1	A0A669KA35
	PCSK5	NM_001190482.2		c.1312+10160G>A		intron	N/A	NP_001177411.1	Q92824-1
	PCSK5	NM_006200.6		c.1312+10160G>A		intron	N/A	NP_006191.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCSK5	ENST00000674117.1	MANE Select	c.1312+10160G>A		intron	N/A	ENSP00000500971.1	A0A669KA35
	PCSK5	ENST00000376752.9	TSL:1	c.1312+10160G>A		intron	N/A	ENSP00000365943.4	Q92824-2
	PCSK5	ENST00000854198.1		c.1312+10160G>A		intron	N/A	ENSP00000524257.1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85871 AN: 151898 Hom.: 25183 Cov.: 33

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.566 AC: 85966 AN: 152016 Hom.: 25221 Cov.: 33 AF XY: 0.567 AC XY: 42130 AN XY: 74302

African (AFR) AF: 0.633 AC: 26276 AN: 41478

American (AMR) AF: 0.644 AC: 9827 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1606 AN: 3472

East Asian (EAS) AF: 0.939 AC: 4853 AN: 5168

South Asian (SAS) AF: 0.596 AC: 2875 AN: 4820

European-Finnish (FIN) AF: 0.425 AC: 4480 AN: 10540

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.505 AC: 34308 AN: 67956

Other (OTH) AF: 0.584 AC: 1235 AN: 2114

Alfa AF: 0.523 Hom.: 29661

Bravo AF: 0.591

Asia WGS AF: 0.742 AC: 2581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.3
DANN	Benign	0.50
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1331384; hg19: chr9-78759288;