NM_005817.5:c.853_855delGGCinsTGT

Variant names:

• chr19-4844773-GCC-ACA
• NM_005817.5:c.853_855delGGCinsTGT
• PLIN3 p.Gly285Cys

Variant summary

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

The NM_005817.5(PLIN3):​c.853_855delGGCinsTGT​(p.Gly285Cys) 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G285D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLIN3 NM_005817.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 0 publications found

Genes affected

PLIN3 (HGNC:16893): (perilipin 3) Mannose 6-phophate receptors (MPRs) deliver lysosomal hydrolase from the Golgi to endosomes and then return to the Golgi complex. The protein encoded by this gene interacts with the cytoplasmic domains of both cation-independent and cation-dependent MPRs, and is required for endosome-to-Golgi transport. This protein also binds directly to the GTPase RAB9 (RAB9A), a member of the RAS oncogene family. The interaction with RAB9 has been shown to increase the affinity of this protein for its cargo. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2009]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005817.5. 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
	PLIN3	NM_005817.5	MANE Select	c.853_855delGGCinsTGT	p.Gly285Cys	missense	N/A	NP_005808.3
	PLIN3	NM_001164189.2		c.853_855delGGCinsTGT	p.Gly285Cys	missense	N/A	NP_001157661.1	O60664-3
	PLIN3	NM_001164194.2		c.817_819delGGCinsTGT	p.Gly273Cys	missense	N/A	NP_001157666.1	O60664-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN3	ENST00000221957.9	TSL:1 MANE Select	c.853_855delGGCinsTGT	p.Gly285Cys	missense	N/A	ENSP00000221957.3	O60664-1
	PLIN3	ENST00000585479.5	TSL:1	c.853_855delGGCinsTGT	p.Gly285Cys	missense	N/A	ENSP00000465596.1	O60664-3
	PLIN3	ENST00000884464.1		c.853_855delGGCinsTGT	p.Gly285Cys	missense	N/A	ENSP00000554523.1

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		1.4

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: chr19-4844785;