19-44944779-TG-AA

Variant names:

• chr19-44944779-TG-AA
• NM_001646.3:c.107_108delTGinsAA
• APOC4 p.Leu36Gln

Variant summary

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

The NM_001646.3(APOC4):​c.107_108delTGinsAA​(p.Leu36Gln) 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: 30)
• Consequence: APOC4 NM_001646.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 0 publications found

Genes affected

APOC4 (HGNC:611): (apolipoprotein C4) This gene encodes a lipid-binding protein belonging to the apolipoprotein gene family. The protein is thought to play a role in lipid metabolism. Polymorphisms in this gene may influence circulating lipid levels and may be associated with coronary artery disease risk. This gene is present in a cluster with other related apolipoprotein genes on chromosome 19. Naturally occurring read-through transcription exists between this gene and the neighboring downstream apolipoprotein C-II (APOC2) gene. [provided by RefSeq, Mar 2011]

APOC4-APOC2 (HGNC:44426): (APOC4-APOC2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring apolipoprotein C-IV (APOC4) and apolipoprotein C-II (APOC2) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001646.3. 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
	APOC4	NM_001646.3	MANE Select	c.107_108delTGinsAA	p.Leu36Gln	missense	N/A	NP_001637.1	P55056
	APOC4-APOC2	NR_037932.1		n.147_148delTGinsAA		non_coding_transcript_exon	Exon 2 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC4	ENST00000592954.2	TSL:1 MANE Select	c.107_108delTGinsAA	p.Leu36Gln	missense	N/A	ENSP00000468236.1	P55056
	APOC4-APOC2	ENST00000589057.5	TSL:5	c.107_108delTGinsAA	p.Leu36Gln	missense	N/A	ENSP00000468139.1	K7ER74
	APOC4	ENST00000896758.1		c.128_129delTGinsAA	p.Leu43Gln	missense	N/A	ENSP00000566817.1

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.0

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: chr19-45448036;