NM_001372043.1:c.1312+6364G>T

Variant names:

• chr9-76140576-G-T
• rs1416325
• NM_001372043.1:c.1312+6364G>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+6364G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 151,928 control chromosomes in the GnomAD database, including 3,867 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 0.19 (3867 hom., cov: 32)
• Consequence: PCSK5 NM_001372043.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 3 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]

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 = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCSK5	NM_001372043.1	c.1312+6364G>T		intron_variant	Intron 10 of 37	ENST00000674117.1	NP_001358972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCSK5	ENST00000674117.1	c.1312+6364G>T		intron_variant	Intron 10 of 37		NM_001372043.1	ENSP00000500971.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28498 AN: 151810 Hom.: 3854 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.188 AC: 28532 AN: 151928 Hom.: 3867 Cov.: 32 AF XY: 0.193 AC XY: 14319 AN XY: 74224

African (AFR) AF: 0.122 AC: 5076 AN: 41468

American (AMR) AF: 0.391 AC: 5962 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 394 AN: 3472

East Asian (EAS) AF: 0.600 AC: 3089 AN: 5148

South Asian (SAS) AF: 0.207 AC: 997 AN: 4810

European-Finnish (FIN) AF: 0.123 AC: 1300 AN: 10562

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11167 AN: 67902

Other (OTH) AF: 0.214 AC: 453 AN: 2114

Alfa AF: 0.186 Hom.: 3216

Bravo AF: 0.211

Asia WGS AF: 0.400 AC: 1385 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.46
PhyloP100		-0.18
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: rs1416325; hg19: chr9-78755492;