Genetic Variant PLIN4:p.Ile748Phe (chr19-4511718-T-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001367868.2(PLIN4):c.2242A>T(p.Ile748Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. I748V) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000054 ( 1 hom., cov: 10)

Exomes 𝑓: 0.000022 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

PLIN4
NM_001367868.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0300

Publications

17 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03300813).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367868.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLIN4	NM_001367868.2	MANE Select	c.2242A>T	p.Ile748Phe	missense	Exon 5 of 8	NP_001354797.1	Q96Q06
PLIN4	NM_001393888.1		c.2245A>T	p.Ile749Phe	missense	Exon 5 of 8	NP_001380817.1	A0A0J9YXN7
PLIN4	NM_001393889.1		c.2245A>T	p.Ile749Phe	missense	Exon 5 of 8	NP_001380818.1	A0A0J9YXN7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLIN4	ENST00000301286.5	TSL:5 MANE Select	c.2242A>T	p.Ile748Phe	missense	Exon 5 of 8	ENSP00000301286.4	Q96Q06
PLIN4	ENST00000966625.1		c.2428A>T	p.Ile810Phe	missense	Exon 6 of 9	ENSP00000636684.1
PLIN4	ENST00000966622.1		c.2425A>T	p.Ile809Phe	missense	Exon 6 of 9	ENSP00000636681.1

Frequencies

GnomAD3 genomes

AF:

0.0000545

AC:

AN:

73386

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00205

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000359

AC:

AN:

222694

AF XY:

0.0000327

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000222

AC:

AN:

1262718

Hom.:

Cov.:

AF XY:

0.0000255

AC XY:

AN XY:

626302

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29446

American (AMR)

AF:

0.00

AC:

AN:

36026

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21616

East Asian (EAS)

AF:

0.00

AC:

AN:

31604

South Asian (SAS)

AF:

0.000383

AC:

AN:

70490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42170

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4934

European-Non Finnish (NFE)

AF:

0.00000102

AC:

AN:

975650

Other (OTH)

AF:

0.00

AC:

AN:

50782

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.620

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000545

AC:

AN:

73444

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

35392

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24278

American (AMR)

AF:

0.00

AC:

AN:

6326

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1692

East Asian (EAS)

AF:

0.00

AC:

AN:

2026

South Asian (SAS)

AF:

0.00206

AC:

AN:

1942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4120

Middle Eastern (MID)

AF:

0.00

AC:

AN:

142

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

31538

Other (OTH)

AF:

0.00

AC:

AN:

964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.700

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

353

ExAC

AF:

0.0000426

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.031

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.069

M_CAP

Benign

0.027

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

-0.030

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.1

REVEL

Benign

0.13

Sift

Uncertain

0.016

Sift4G

Uncertain

0.013

Polyphen

0.0070

Vest4

0.24

MutPred

0.40

Gain of ubiquitination at K731 (P = 0.1062)

MVP

0.030

ClinPred

0.056

GERP RS

4.6

Varity_R

0.076

gMVP

0.046

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over