19-1481810-AC-GT

Variant names:

• chr19-1481810-AC-GT
• NM_017573.5:c.2216_2217delGTinsAC
• PCSK4 p.Arg739His

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_017573.5(PCSK4):​c.2216_2217delGTinsAC​(p.Arg739His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PCSK4 NM_017573.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.937
• Publications: 0 publications found

Genes affected

PCSK4 (HGNC:8746): (proprotein convertase subtilisin/kexin type 4) 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 subcellular compartments where a second autocatalytic even takes place and the catalytic activity is acquired. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. The protease is expressed only in the testis, placenta, and ovary. It plays a critical role in fertilization, fetoplacental growth, and embryonic development and processes multiple prohormones including pro-pituitary adenylate cyclase-activating protein and pro-insulin-like growth factor II. [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017573.5. 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
	PCSK4	NM_017573.5	MANE Select	c.2216_2217delGTinsAC	p.Arg739His	missense	N/A	NP_060043.2	Q6UW60-1
	PCSK4	NM_001395257.1		c.*390_*391delGTinsAC		3_prime_UTR	Exon 14 of 14	NP_001382186.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCSK4	ENST00000300954.10	TSL:1 MANE Select	c.2216_2217delGTinsAC	p.Arg739His	missense	N/A	ENSP00000300954.5	Q6UW60-1
	PCSK4	ENST00000883590.1		c.2189_2190delGTinsAC	p.Arg730His	missense	N/A	ENSP00000553649.1
	PCSK4	ENST00000441747.6	TSL:2	n.2258_2259delGTinsAC		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.94

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-1481809;