rs7034265

Variant names:

• chr9-76356337-T-C
• rs7034265
• NM_001372043.1:c.5254+2118T>C

Variant summary

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

The NM_001372043.1(PCSK5):​c.5254+2118T>C 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 152,190 control chromosomes in the GnomAD database, including 3,198 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 (3198 hom., cov: 33)
• Consequence: PCSK5 NM_001372043.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCSK5	NM_001372043.1	c.5254+2118T>C		intron_variant	Intron 37 of 37	ENST00000674117.1	NP_001358972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCSK5	ENST00000674117.1	c.5254+2118T>C		intron_variant	Intron 37 of 37		NM_001372043.1	ENSP00000500971.1
PCSK5	ENST00000545128.5	c.5173+2118T>C		intron_variant	Intron 36 of 36	5		ENSP00000446280.1
PCSK5	ENST00000424854.6	c.4273+2118T>C		intron_variant	Intron 30 of 30	5		ENSP00000411654.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30770 AN: 152072 Hom.: 3199 Cov.: 33

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.202 AC: 30786 AN: 152190 Hom.: 3198 Cov.: 33 AF XY: 0.203 AC XY: 15112 AN XY: 74412

African (AFR) AF: 0.237 AC: 9845 AN: 41508

American (AMR) AF: 0.163 AC: 2486 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3468

East Asian (EAS) AF: 0.240 AC: 1242 AN: 5182

South Asian (SAS) AF: 0.210 AC: 1011 AN: 4820

European-Finnish (FIN) AF: 0.192 AC: 2036 AN: 10604

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12843 AN: 67998

Other (OTH) AF: 0.218 AC: 461 AN: 2116

Alfa AF: 0.195 Hom.: 12839

Bravo AF: 0.201

Asia WGS AF: 0.203 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.74
PhyloP100		-0.097
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: rs7034265; hg19: chr9-78971253;