rs8029797

Variant names:

• chr15-101365954-T-A
• rs8029797
• NM_002570.5:c.1858+242A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-101365954-T-A
• chr15-101365954-T-C
• chr15-101365954-T-G

Variant summary

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

The NM_002570.5(PCSK6):​c.1858+242A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 356,284 control chromosomes in the GnomAD database, including 28,071 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 0.40 (13636 hom., cov: 32)
  • Exomes 𝑓: 0.36 (14435 hom.)
• Consequence: PCSK6 NM_002570.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• Publications: 2 publications found

Genes affected

PCSK6 (HGNC:8569): (proprotein convertase subtilisin/kexin type 6) 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 and sorts to the trans-Golgi network where a second autocatalytic event takes place and the catalytic activity is acquired. The encoded protease is constitutively secreted into the extracellular matrix and expressed in many tissues, including neuroendocrine, liver, gut, and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. Some of its substrates include transforming growth factor beta related proteins, proalbumin, and von Willebrand factor. This gene is thought to play a role in tumor progression and left-right patterning. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Feb 2014]

PCSK6 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: Unknown 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002570.5. 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
	PCSK6	NM_002570.5	MANE Select	c.1858+242A>T		intron	N/A	NP_002561.1	P29122-1
	PCSK6	NM_138319.4		c.1858+242A>T		intron	N/A	NP_612192.1	P29122-2
	PCSK6	NM_001291309.2		c.1636+242A>T		intron	N/A	NP_001278238.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCSK6	ENST00000611716.5	TSL:1 MANE Select	c.1858+242A>T		intron	N/A	ENSP00000482760.1	P29122-1
	PCSK6	ENST00000622483.4	TSL:1	c.1858+242A>T		intron	N/A	ENSP00000481556.1	A0A087WY68
	PCSK6	ENST00000619160.4	TSL:1	c.1858+242A>T		intron	N/A	ENSP00000482831.1	A0A087WZR0

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61202 AN: 151860 Hom.: 13603 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.376

GnomAD4 exome AF: 0.357 AC: 72999 AN: 204306 Hom.: 14435 Cov.: 4 AF XY: 0.351 AC XY: 36786 AN XY: 104856

African (AFR) AF: 0.568 AC: 3312 AN: 5836

American (AMR) AF: 0.577 AC: 3483 AN: 6036

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 2109 AN: 7326

East Asian (EAS) AF: 0.602 AC: 9612 AN: 15964

South Asian (SAS) AF: 0.190 AC: 1883 AN: 9934

European-Finnish (FIN) AF: 0.322 AC: 4300 AN: 13368

Middle Eastern (MID) AF: 0.276 AC: 290 AN: 1052

European-Non Finnish (NFE) AF: 0.328 AC: 43298 AN: 131860

Other (OTH) AF: 0.364 AC: 4712 AN: 12930

GnomAD4 genome AF: 0.403 AC: 61295 AN: 151978 Hom.: 13636 Cov.: 32 AF XY: 0.400 AC XY: 29714 AN XY: 74264

African (AFR) AF: 0.559 AC: 23166 AN: 41434

American (AMR) AF: 0.512 AC: 7825 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 963 AN: 3468

East Asian (EAS) AF: 0.577 AC: 2984 AN: 5168

South Asian (SAS) AF: 0.181 AC: 871 AN: 4808

European-Finnish (FIN) AF: 0.296 AC: 3125 AN: 10544

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21283 AN: 67958

Other (OTH) AF: 0.373 AC: 783 AN: 2102

Alfa AF: 0.346 Hom.: 1216

Bravo AF: 0.439

Asia WGS AF: 0.358 AC: 1249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.76
PhyloP100		-2.3
PromoterAI		-0.034	Neutral
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: rs8029797; hg19: chr15-101906159;