chr15-89665720-C-T

Variant names:

• chr15-89665720-C-T
• rs1345627727
• NM_002666.5:c.1432G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002666.5(PLIN1):​c.1432G>A​(p.Ala478Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,306,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: PLIN1 NM_002666.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.761
• Publications: 1 publications found

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]

PLIN1 Gene-Disease associations (from GenCC):

• PLIN1-related familial partial lipodystrophy

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04956919).
• BS2: High AC in GnomAdExome4 at 16 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002666.5. 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
	PLIN1	NM_002666.5	MANE Select	c.1432G>A	p.Ala478Thr	missense	Exon 9 of 9	NP_002657.3	O60240
	PLIN1	NM_001145311.2		c.1432G>A	p.Ala478Thr	missense	Exon 9 of 9	NP_001138783.1	O60240

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN1	ENST00000300055.10	TSL:1 MANE Select	c.1432G>A	p.Ala478Thr	missense	Exon 9 of 9	ENSP00000300055.5	O60240
	PLIN1	ENST00000896664.1		c.1540G>A	p.Ala514Thr	missense	Exon 9 of 9	ENSP00000566723.1
	PLIN1	ENST00000896666.1		c.1462G>A	p.Ala488Thr	missense	Exon 9 of 9	ENSP00000566725.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000124 AC: 1 AN: 80454 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000342

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000122 AC: 16 AN: 1306744 Hom.: 0 Cov.: 31 AF XY: 0.0000109 AC XY: 7 AN XY: 643884

African (AFR) AF: 0.00 AC: 0 AN: 26694

American (AMR) AF: 0.00 AC: 0 AN: 27462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23072

East Asian (EAS) AF: 0.00 AC: 0 AN: 28722

South Asian (SAS) AF: 0.00 AC: 0 AN: 71022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3812

European-Non Finnish (NFE) AF: 0.0000154 AC: 16 AN: 1039290

Other (OTH) AF: 0.00 AC: 0 AN: 53776

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.79
DANN	Benign	0.95
DEOGEN2	Benign	0.096	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.76
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.014
Sift	Benign	0.32	T
Sift4G	Benign	0.44	T
Polyphen		0.059	B
Vest4		0.067
MutPred		0.12		Gain of relative solvent accessibility (P = 0.0023)
MVP		0.014
MPC		1.2
ClinPred		0.10	T
GERP RS		-4.0
Varity_R		0.058
gMVP		0.098
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1345627727; hg19: chr15-90208951;