19-4504569-C-A

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

5
14

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

Genome browser will be placed here

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
PLIN4NM_001367868.2 linkc.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
PLIN4ENST00000301286.5 linkc.4006G>T p.Gly1336Cys missense_variant Exon 8 of 8 5 NM_001367868.2 ENSP00000301286.4 Q96Q06
PLIN4ENST00000633942.1 linkc.4009G>T p.Gly1337Cys missense_variant Exon 8 of 8 5 ENSP00000488481.1 A0A0J9YXN7

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000451
AC:
1
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:
4
AN:
1450296
Hom.:
0
Cov.:
31
AF XY:
0.00000416
AC XY:
3
AN XY:
721118
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33254
American (AMR)
AF:
0.00
AC:
0
AN:
43862
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25862
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39190
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85036
European-Finnish (FIN)
AF:
0.0000829
AC:
4
AN:
48256
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5740
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1109124
Other (OTH)
AF:
0.00
AC:
0
AN:
59972
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.463
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

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
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
10
DANN
Uncertain
0.99
DEOGEN2
Benign
0.018
T;.
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.61
FATHMM_MKL
Benign
0.027
N
LIST_S2
Benign
0.56
T;T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.30
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
M;.
PhyloP100
-0.64
PrimateAI
Benign
0.33
T
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
D
GERP RS
0.56
Varity_R
0.32
gMVP
0.10
Mutation Taster
=98/2
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

Publications

Other links and lift over

dbSNP: rs1159663200; hg19: chr19-4504581; API