22-36199373-CAC-AAG

Variant names:

• chr22-36199373-CAC-AAG
• NM_001386885.1:c.37_39delGTGinsCTT
• APOL4 p.Val13Leu

Variant summary

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

The NM_001386885.1(APOL4):​c.37_39delGTGinsCTT​(p.Val13Leu) variant causes a missense, splice region 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. V13M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: APOL4 NM_001386885.1 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540
• Publications: 0 publications found

Genes affected

APOL4 (HGNC:14867): (apolipoprotein L4) This gene encodes a member of the apolipoprotein L family. The encoded protein may play a role in lipid exchange and transport throughout the body, as well as in reverse cholesterol transport from peripheral cells to the liver. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2020]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386885.1. 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
	APOL4	NM_001386885.1	MANE Select	c.37_39delGTGinsCTT	p.Val13Leu	missense splice_region	N/A	NP_001373814.1	Q9BPW4-2
	APOL4	NM_145660.2		c.46_48delGTGinsCTT	p.Val16Leu	missense splice_region	N/A	NP_663693.1	Q9BPW4-1
	APOL4	NM_030643.4		c.37_39delGTGinsCTT	p.Val13Leu	missense splice_region	N/A	NP_085146.2	Q9BPW4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL4	ENST00000683024.1	MANE Select	c.37_39delGTGinsCTT	p.Val13Leu	missense splice_region	N/A	ENSP00000507418.1	Q9BPW4-2
	APOL4	ENST00000352371.5	TSL:1	c.46_48delGTGinsCTT	p.Val16Leu	missense splice_region	N/A	ENSP00000338260.3	Q9BPW4-1
	APOL4	ENST00000616056.4	TSL:1	c.37_39delGTGinsCTT	p.Val13Leu	missense splice_region	N/A	ENSP00000483497.1	Q9BPW4-2

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		0.054

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: chr22-36595419;