15-89673353-C-T

Position:

• chr15-89673353-C-T

Variant summary

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

The NM_002666.5(PLIN1):​c.107G>A​(p.Cys36Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C36F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLIN1 NM_002666.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLIN1	NM_002666.5	c.107G>A	p.Cys36Tyr	missense_variant	3/9	ENST00000300055.10
PLIN1	NM_001145311.2	c.107G>A	p.Cys36Tyr	missense_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLIN1	ENST00000300055.10	c.107G>A	p.Cys36Tyr	missense_variant	3/9	1	NM_002666.5	P1
PLIN1	ENST00000430628.2	c.107G>A	p.Cys36Tyr	missense_variant	3/9	5		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.36	N
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.42	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;M
MutationTaster	Benign	0.79	N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.097
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	D;D
Vest4		0.49
MutPred		0.31		Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);
MVP		0.40
MPC		0.20
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.37
gMVP		0.51

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: rs140081686; hg19: chr15-90216584;