15-89670112-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002666.5(PLIN1):​c.466G>A​(p.Val156Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,728 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V156L) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PLIN1
NM_002666.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.219
Variant links:
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_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06496993).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLIN1NM_002666.5 linkc.466G>A p.Val156Met missense_variant Exon 5 of 9 ENST00000300055.10 NP_002657.3 O60240
PLIN1NM_001145311.2 linkc.466G>A p.Val156Met missense_variant Exon 5 of 9 NP_001138783.1 O60240

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLIN1ENST00000300055.10 linkc.466G>A p.Val156Met missense_variant Exon 5 of 9 1 NM_002666.5 ENSP00000300055.5 O60240
PLIN1ENST00000430628.2 linkc.466G>A p.Val156Met missense_variant Exon 5 of 9 5 ENSP00000402167.2 O60240

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461728
Hom.:
0
Cov.:
35
AF XY:
0.00000138
AC XY:
1
AN XY:
727156
show subpopulations
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:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
8.3
DANN
Benign
0.95
DEOGEN2
Benign
0.096
T;T
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.69
.;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.065
T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.21
N;N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.85
N;N
REVEL
Benign
0.060
Sift
Benign
0.31
T;T
Sift4G
Benign
0.30
T;T
Polyphen
0.043
B;B
Vest4
0.086
MutPred
0.63
Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP
0.014
MPC
0.027
ClinPred
0.093
T
GERP RS
0.41
Varity_R
0.038
gMVP
0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-90213343; API