dbSNP rs377657199: PLIN5:p.Arg334Leu (chr19-4523919-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001013706.3(PLIN5):c.1001G>T(p.Arg334Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,374,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R334C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

PLIN5
NM_001013706.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.339

Publications

0 publications found

Variant links:

Genes affected

PLIN5 (HGNC:33196): (perilipin 5) Predicted to enable identical protein binding activity and lipase binding activity. Predicted to be involved in several processes, including negative regulation of peroxisome proliferator activated receptor signaling pathway; regulation of lipase activity; and regulation of lipid metabolic process. Located in intracellular membrane-bounded organelle and lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

PLIN5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013706.3. 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
	PLIN5	NM_001013706.3	MANE Select	c.1001G>T	p.Arg334Leu	missense	Exon 8 of 8	NP_001013728.2	Q00G26

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLIN5	ENST00000381848.7	TSL:1 MANE Select	c.1001G>T	p.Arg334Leu	missense	Exon 8 of 8	ENSP00000371272.2	Q00G26
PLIN5	ENST00000905186.1		c.1238G>T	p.Arg413Leu	missense	Exon 9 of 9	ENSP00000575245.1
PLIN5	ENST00000905182.1		c.1202G>T	p.Arg401Leu	missense	Exon 9 of 9	ENSP00000575241.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.27e-7

AC:

AN:

1374702

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

678964

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29364

American (AMR)

AF:

0.00

AC:

AN:

33950

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24414

East Asian (EAS)

AF:

0.00

AC:

AN:

34534

South Asian (SAS)

AF:

0.00

AC:

AN:

77888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33834

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5492

European-Non Finnish (NFE)

AF:

9.28e-7

AC:

AN:

1077836

Other (OTH)

AF:

0.00

AC:

AN:

57390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.011

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.51

M_CAP

Benign

0.070

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.5

PhyloP100

-0.34

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.074

Sift

Benign

0.40

Sift4G

Benign

0.70

Polyphen

0.28

Vest4

0.34

MutPred

0.52

Loss of MoRF binding (P = 0.0265)

MVP

0.20

MPC

0.46

ClinPred

0.22

GERP RS

1.7

Varity_R

0.085

gMVP

0.29

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.25

Position offset: -10

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over