chr15-89665842-CCA-C
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Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_002666.5(PLIN1):c.1308_1309delTG(p.Pro439fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000763 in 1,311,090 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.6e-7 ( 0 hom. )
Consequence
PLIN1
NM_002666.5 frameshift
NM_002666.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.920
Genes affected
PLIN1 (HGNC:9076): (perilipin 1) The protein encoded by this gene coats lipid storage droplets in adipocytes, thereby protecting them until they can be broken down by hormone-sensitive lipase. The encoded protein is the major cAMP-dependent protein kinase substrate in adipocytes and, when unphosphorylated, may play a role in the inhibition of lipolysis. Alternatively spliced transcript variants varying in the 5' UTR, but encoding the same protein, have been found for this gene. [provided by RefSeq, Feb 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.166 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 15-89665842-CCA-C is Pathogenic according to our data. Variant chr15-89665842-CCA-C is described in ClinVar as [Pathogenic]. Clinvar id is 1342123.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLIN1 | NM_002666.5 | c.1308_1309delTG | p.Pro439fs | frameshift_variant | 9/9 | ENST00000300055.10 | NP_002657.3 | |
PLIN1 | NM_001145311.2 | c.1308_1309delTG | p.Pro439fs | frameshift_variant | 9/9 | NP_001138783.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLIN1 | ENST00000300055.10 | c.1308_1309delTG | p.Pro439fs | frameshift_variant | 9/9 | 1 | NM_002666.5 | ENSP00000300055.5 | ||
PLIN1 | ENST00000430628.2 | c.1308_1309delTG | p.Pro439fs | frameshift_variant | 9/9 | 5 | ENSP00000402167.2 | |||
PLIN1 | ENST00000560330.1 | c.124-903_124-902delTG | intron_variant | 5 | ENSP00000453426.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 7.63e-7 AC: 1AN: 1311090Hom.: 0 AF XY: 0.00000155 AC XY: 1AN XY: 643966
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
PLIN1-related familial partial lipodystrophy Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 21, 2022 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.