19-4504662-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001367868.2(PLIN4):c.3913G>A(p.Ala1305Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,450,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3555024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLIN4	NM_001367868.2	c.3913G>A	p.Ala1305Thr	missense_variant	8/8	ENST00000301286.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLIN4	ENST00000301286.5	c.3913G>A	p.Ala1305Thr	missense_variant	8/8	5	NM_001367868.2	P1
PLIN4	ENST00000633942.1	c.3916G>A	p.Ala1306Thr	missense_variant	8/8	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450698 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721704

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.3871G>A (p.A1291T) alteration is located in exon 6 (coding exon 6) of the PLIN4 gene. This alteration results from a G to A substitution at nucleotide position 3871, causing the alanine (A) at amino acid position 1291 to be replaced by a threonine (T). 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	0.28
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.062	T;.
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.064
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.67	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.9	D;.
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.31
MutPred		0.48		Gain of phosphorylation at A1291 (P = 0.1274);.;
MVP		0.21
ClinPred		0.96	D
GERP RS		4.4
Varity_R		0.39
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-4504674;