chr17-66220696-ACG-TAA

Variant names:

• chr17-66220696-ACG-TAA
• NM_000042.3:c.460_462delCGTinsTTA
• APOH p.Arg154Leu

Variant summary

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

The NM_000042.3(APOH):​c.460_462delCGTinsTTA​(p.Arg154Leu) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R154H) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: APOH NM_000042.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.491
• Publications: 0 publications found

Genes affected

APOH (HGNC:616): (apolipoprotein H) Apolipoprotein H, also known as beta-2-glycoprotein I, is a component of circulating plasma lipoproteins. It has been implicated in a variety of physiologic pathways including lipoprotein metabolism, coagulation, hemostasis, and the production of antiphospholipid autoantibodies. APOH may be a required cofactor for anionic phospholipid binding by the antiphospholipid autoantibodies found in sera of many patients with lupus and primary antiphospholipid syndrome (APS). The anti-beta (2) glycoprotein I antibodies from APS patients, mediate inhibition of activated protein C which has anticoagulant properties. Because beta-2-GPI is the main autoantigen in patients with APS, the disruption of this pathway by autoantibodies may be an important mechanism for thrombosis in patients with APS.[provided by RefSeq, Dec 2019]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000042.3. 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
	APOH	NM_000042.3	MANE Select	c.460_462delCGTinsTTA	p.Arg154Leu	missense	N/A	NP_000033.2	A0A384NKM6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOH	ENST00000205948.11	TSL:1 MANE Select	c.460_462delCGTinsTTA	p.Arg154Leu	missense	N/A	ENSP00000205948.6	P02749
	APOH	ENST00000879124.1		c.460_462delCGTinsTTA	p.Arg154Leu	missense	N/A	ENSP00000549183.1
	APOH	ENST00000879112.1		c.460_462delCGTinsTTA	p.Arg154Leu	missense	N/A	ENSP00000549171.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49

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: chr17-64216814;