22-36141536-AA-GT

Variant names:

• chr22-36141536-AA-GT
• NM_145639.2:c.659_660delTTinsAC
• APOL3 p.Ile220Asn

Variant summary

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

The NM_145639.2(APOL3):​c.659_660delTTinsAC​(p.Ile220Asn) 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. I220T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: APOL3 NM_145639.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 0 publications found

Genes affected

APOL3 (HGNC:14868): (apolipoprotein L3) This gene is a member of the apolipoprotein L gene family, and it is present in a cluster with other family members on chromosome 22. The encoded protein is found in the cytoplasm, where it may affect the movement of lipids, including cholesterol, and/or allow the binding of lipids to organelles. In addition, expression of this gene is up-regulated by tumor necrosis factor-alpha in endothelial cells lining the normal and atherosclerotic iliac artery and aorta. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145639.2. 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
	APOL3	NM_145639.2	MANE Select	c.659_660delTTinsAC	p.Ile220Asn	missense	N/A	NP_663614.1	O95236-2
	APOL3	NM_145640.2		c.872_873delTTinsAC	p.Ile291Asn	missense	N/A	NP_663615.1	O95236-1
	APOL3	NM_001393587.1		c.662_663delTTinsAC	p.Ile221Asn	missense	N/A	NP_001380516.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL3	ENST00000424878.4	TSL:1 MANE Select	c.659_660delTTinsAC	p.Ile220Asn	missense	N/A	ENSP00000415779.3	O95236-2
	APOL3	ENST00000349314.7	TSL:1	c.872_873delTTinsAC	p.Ile291Asn	missense	N/A	ENSP00000344577.2	O95236-1
	APOL3	ENST00000361710.6	TSL:1	c.272_273delTTinsAC	p.Ile91Asn	missense	N/A	ENSP00000355164.2	O95236-3

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		1.1

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: chr22-36537584;