chr15-89665842-C-G

Variant names:

• chr15-89665842-C-G
• rs766044739
• NM_002666.5:c.1310G>C

Variant summary

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

The NM_002666.5(PLIN1):​c.1310G>C​(p.Gly437Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: 32)
• Consequence: PLIN1 NM_002666.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361

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=0.1035305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN1	NM_002666.5	c.1310G>C	p.Gly437Ala	missense_variant	Exon 9 of 9	ENST00000300055.10	NP_002657.3
PLIN1	NM_001145311.2	c.1310G>C	p.Gly437Ala	missense_variant	Exon 9 of 9		NP_001138783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN1	ENST00000300055.10	c.1310G>C	p.Gly437Ala	missense_variant	Exon 9 of 9	1	NM_002666.5	ENSP00000300055.5
PLIN1	ENST00000430628.2	c.1310G>C	p.Gly437Ala	missense_variant	Exon 9 of 9	5		ENSP00000402167.2
PLIN1	ENST00000560330.1	c.124-901G>C		intron_variant	Intron 2 of 2	5		ENSP00000453426.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.1
DANN	Benign	0.73
DEOGEN2	Benign	0.18	T;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.52	.;T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.34	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.042	D;D
Polyphen		0.0050	B;B
Vest4		0.086
MutPred		0.14		Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);
MVP		0.014
MPC		1.3
ClinPred		0.13	T
GERP RS		3.1
Varity_R		0.068
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs766044739; hg19: chr15-90209073;