6-160586504-GAG-AAT

Variant names:

• chr6-160586504-GAG-AAT
• NM_005577.4:c.4072_4074delCTCinsATT
• LPA p.Leu1358Ile

Variant summary

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

The NM_005577.4(LPA):​c.4072_4074delCTCinsATT​(p.Leu1358Ile) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LPA NM_005577.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 0 publications found

Genes affected

LPA (HGNC:6667): (lipoprotein(a)) The protein encoded by this gene is a serine proteinase that inhibits the activity of tissue-type plasminogen activator I. The encoded protein constitutes a substantial portion of lipoprotein(a) and is proteolytically cleaved, resulting in fragments that attach to atherosclerotic lesions and promote thrombogenesis. Elevated plasma levels of this protein are linked to atherosclerosis. Depending on the individual, the encoded protein contains 2-43 copies of kringle-type domains. The allele represented here contains 15 copies of the kringle-type repeats and corresponds to that found in the reference genome sequence. [provided by RefSeq, Dec 2009]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005577.4. 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
	LPA	NM_005577.4	MANE Select	c.4072_4074delCTCinsATT	p.Leu1358Ile	missense	N/A	NP_005568.2	P08519

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPA	ENST00000316300.10	TSL:1 MANE Select	c.4072_4074delCTCinsATT	p.Leu1358Ile	missense	N/A	ENSP00000321334.6	P08519
	LPA	ENST00000870146.1		c.4069_4071delCTCinsATT	p.Leu1357Ile	missense	N/A	ENSP00000540205.1
	LPA	ENST00000870147.1		c.3754_3756delCTCinsATT	p.Leu1252Ile	missense	N/A	ENSP00000540206.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.066

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: chr6-161007536;