15-89667753-G-T

Variant names:

• chr15-89667753-G-T
• NM_002666.5:c.812C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002666.5(PLIN1):​c.812C>A​(p.Ala271Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,411,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PLIN1 NM_002666.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18076527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN1	NM_002666.5	c.812C>A	p.Ala271Glu	missense_variant	Exon 7 of 9	ENST00000300055.10	NP_002657.3
PLIN1	NM_001145311.2	c.812C>A	p.Ala271Glu	missense_variant	Exon 7 of 9		NP_001138783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN1	ENST00000300055.10	c.812C>A	p.Ala271Glu	missense_variant	Exon 7 of 9	1	NM_002666.5	ENSP00000300055.5
PLIN1	ENST00000430628.2	c.812C>A	p.Ala271Glu	missense_variant	Exon 7 of 9	5		ENSP00000402167.2
PLIN1	ENST00000560330.1	c.-113C>A		upstream_gene_variant		5		ENSP00000453426.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1411626 Hom.: 0 Cov.: 34 AF XY: 0.00000143 AC XY: 1 AN XY: 697270

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000203

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.89
DEOGEN2	Benign	0.063	T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.58	N;N
REVEL	Benign	0.068
Sift	Benign	0.43	T;T
Sift4G	Uncertain	0.048	D;D
Polyphen		0.74	P;P
Vest4		0.22
MutPred		0.50		Loss of loop (P = 0.0153);Loss of loop (P = 0.0153);
MVP		0.048
MPC		0.081
ClinPred		0.17	T
GERP RS		2.3
Varity_R		0.062
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-90210984; COSMIC: COSV55584654; COSMIC: COSV55584654;