19-4523716-C-T

Variant names:

• chr19-4523716-C-T
• NM_001013706.3:c.1204G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001013706.3(PLIN5):​c.1204G>A​(p.Gly402Ser) 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. 15/21 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. G402C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLIN5 NM_001013706.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378

Genes affected

PLIN5 (HGNC:33196): (perilipin 5) Predicted to enable identical protein binding activity and lipase binding activity. Predicted to be involved in several processes, including negative regulation of peroxisome proliferator activated receptor signaling pathway; regulation of lipase activity; and regulation of lipid metabolic process. Located in intracellular membrane-bounded organelle and lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047782153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN5	NM_001013706.3	c.1204G>A	p.Gly402Ser	missense_variant	Exon 8 of 8	ENST00000381848.7	NP_001013728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN5	ENST00000381848.7	c.1204G>A	p.Gly402Ser	missense_variant	Exon 8 of 8	1	NM_001013706.3	ENSP00000371272.2
PLIN5	ENST00000589728.1	n.*193G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.7
DANN	Benign	0.82
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.037
Sift	Benign	0.042	D
Sift4G	Uncertain	0.053	T
Polyphen		0.020	B
Vest4		0.12
MutPred		0.22		Gain of glycosylation at G402 (P = 0.044);
MVP		0.13
MPC		0.21
ClinPred		0.053	T
GERP RS		2.5
Varity_R		0.027
gMVP		0.29

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: chr19-4523728;