Genetic Variant PLIN4:p.Ala1296Thr (chr19-4504689-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001367868.2(PLIN4):c.3886G>A(p.Ala1296Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000225 in 1,600,826 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 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. A1296P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 1 hom. )

Consequence

PLIN4
NM_001367868.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.023657382).

BS2

High AC in GnomAdExome4 at 32 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN4	NM_001367868.2 link	c.3886G>A	p.Ala1296Thr	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.3886G>A	p.Ala1296Thr	missense_variant	Exon 8 of 8	5	NM_001367868.2	ENSP00000301286.4		Q96Q06
PLIN4	ENST00000633942.1 link	c.3889G>A	p.Ala1297Thr	missense_variant	Exon 8 of 8	5		ENSP00000488481.1		A0A0J9YXN7

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000495

AC:

AN:

222132

AF XY:

0.0000568

show subpopulations

Gnomad AFR exome

AF:

0.000319

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000221

AC:

AN:

1448600

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

720542

show subpopulations

African (AFR)

AF:

0.000240

AC:

AN:

33394

American (AMR)

AF:

0.00

AC:

AN:

43966

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25936

East Asian (EAS)

AF:

0.00

AC:

AN:

39456

South Asian (SAS)

AF:

0.000222

AC:

AN:

85416

European-Finnish (FIN)

AF:

0.0000222

AC:

AN:

44944

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1109724

Other (OTH)

AF:

0.0000333

AC:

AN:

60004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000672

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.5

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0086

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.58

N;.

PhyloP100

-1.3

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.94

N;.

REVEL

Benign

0.016

Sift

Benign

0.92

T;.

Sift4G

Benign

0.79

T;T

Polyphen

0.054

B;.

Vest4

0.028

MutPred

0.25

Loss of helix (P = 0.1706);.;

MVP

0.030

ClinPred

0.054

GERP RS

-5.1

Varity_R

0.048

gMVP

0.043

Mutation Taster

=100/0

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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19-4504689-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over