Genetic Variant PLIN4:p.Gly1336Cys (chr19-4504569-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001367868.2(PLIN4):c.4006G>T(p.Gly1336Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,450,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. G1336S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

PLIN4
NM_001367868.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.638

Publications

0 publications found

Variant links:

Genes affected

PLIN4 (HGNC:29393): (perilipin 4) Members of the perilipin family, such as PLIN4, coat intracellular lipid storage droplets (Wolins et al., 2003 [PubMed 12840023]).[supplied by OMIM, Feb 2010]

PLIN4 Gene-Disease associations (from GenCC):

vacuolar Neuromyopathy
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

PLIN4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29862505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN4	NM_001367868.2 link	c.4006G>T	p.Gly1336Cys	missense_variant	Exon 8 of 8	ENST00000301286.5	NP_001354797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN4	ENST00000301286.5 link	c.4006G>T	p.Gly1336Cys	missense_variant	Exon 8 of 8	5	NM_001367868.2	ENSP00000301286.4		Q96Q06
PLIN4	ENST00000633942.1 link	c.4009G>T	p.Gly1337Cys	missense_variant	Exon 8 of 8	5		ENSP00000488481.1		A0A0J9YXN7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000451

AC:

AN:

221522

AF XY:

0.00000813

show subpopulations

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:

0.0000592

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1450296

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

721118

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33254

American (AMR)

AF:

0.00

AC:

AN:

43862

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25862

East Asian (EAS)

AF:

0.00

AC:

AN:

39190

South Asian (SAS)

AF:

0.00

AC:

AN:

85036

European-Finnish (FIN)

AF:

0.0000829

AC:

AN:

48256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109124

Other (OTH)

AF:

0.00

AC:

AN:

59972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.56

T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

M;.

PhyloP100

-0.64

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.8

D;.

REVEL

Benign

0.039

Sift

Uncertain

0.010

D;.

Sift4G

Uncertain

0.010

D;D

Polyphen

1.0

D;.

Vest4

0.19

MutPred

0.45

Loss of disorder (P = 0.0172);.;

MVP

0.17

ClinPred

0.62

GERP RS

0.56

Varity_R

0.32

gMVP

0.10

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over