NM_001367868.2:c.4009G>T

Variant names:

• chr19-4504566-C-A
• NM_001367868.2:c.4009G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367868.2(PLIN4):​c.4009G>T​(p.Val1337Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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)
• Consequence: PLIN4 NM_001367868.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0640
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09089163).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN4	NM_001367868.2	c.4009G>T	p.Val1337Leu	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	c.4009G>T	p.Val1337Leu	missense_variant	Exon 8 of 8	5	NM_001367868.2	ENSP00000301286.4
PLIN4	ENST00000633942.1	c.4012G>T	p.Val1338Leu	missense_variant	Exon 8 of 8	5		ENSP00000488481.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3967G>T (p.V1323L) alteration is located in exon 6 (coding exon 6) of the PLIN4 gene. This alteration results from a G to T substitution at nucleotide position 3967, causing the valine (V) at amino acid position 1323 to be replaced by a leucine (L). 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	0.25
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.86
DANN	Benign	0.78
DEOGEN2	Benign	0.0076	T;.
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.
PhyloP100		-0.064
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.8	N;.
REVEL	Benign	0.029
Sift	Benign	0.23	T;.
Sift4G	Benign	0.57	T;T
Polyphen		0.022	B;.
Vest4		0.076
MutPred		0.48		Gain of disorder (P = 0.1429);.;
MVP		0.067
ClinPred		0.20	T
GERP RS		1.1
Varity_R		0.079
gMVP		0.11
Mutation Taster		=92/8	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

Other links and lift over

hg19: chr19-4504578;