Genetic Variant NM_001367868.2:c.3970G>C (chr19-4504605-C-G) – 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.3970G>C(p.Glu1324Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PLIN4
NM_001367868.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

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:

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=0.3077467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN4	NM_001367868.2 link	c.3970G>C	p.Glu1324Gln	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.3970G>C	p.Glu1324Gln	missense_variant	Exon 8 of 8	5	NM_001367868.2	ENSP00000301286.4		Q96Q06
PLIN4	ENST00000633942.1 link	c.3973G>C	p.Glu1325Gln	missense_variant	Exon 8 of 8	5		ENSP00000488481.1		A0A0J9YXN7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000439

AC:

AN:

227630

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000580

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1452096

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722216

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33362

American (AMR)

AF:

0.00

AC:

AN:

44146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25934

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39466

South Asian (SAS)

AF:

0.00

AC:

AN:

85348

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109904

Other (OTH)

AF:

0.00

AC:

AN:

60078

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 12, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.3928G>C (p.E1310Q) alteration is located in exon 6 (coding exon 6) of the PLIN4 gene. This alteration results from a G to C substitution at nucleotide position 3928, causing the glutamic acid (E) at amino acid position 1310 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.011

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.082

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;.

PhyloP100

3.4

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.2

N;.

REVEL

Benign

0.061

Sift

Benign

0.039

D;.

Sift4G

Uncertain

0.036

D;D

Polyphen

0.97

D;.

Vest4

0.25

MutPred

0.32

Loss of phosphorylation at S1307 (P = 0.0955);.;

MVP

0.15

ClinPred

0.90

GERP RS

3.6

Varity_R

0.21

gMVP

0.21

Mutation Taster

=96/4

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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NM_001367868.2:c.3970G>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over