19-4523611-C-T

Variant names:

• chr19-4523611-C-T
• rs755684879
• NM_001013706.3:c.1309G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001013706.3(PLIN5):​c.1309G>A​(p.Val437Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,544 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V437F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PLIN5 NM_001013706.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03965801).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013706.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN5	NM_001013706.3	MANE Select	c.1309G>A	p.Val437Ile	missense	Exon 8 of 8	NP_001013728.2	Q00G26

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN5	ENST00000381848.7	TSL:1 MANE Select	c.1309G>A	p.Val437Ile	missense	Exon 8 of 8	ENSP00000371272.2	Q00G26
	PLIN5	ENST00000905186.1		c.1546G>A	p.Val516Ile	missense	Exon 9 of 9	ENSP00000575245.1
	PLIN5	ENST00000905182.1		c.1510G>A	p.Val504Ile	missense	Exon 9 of 9	ENSP00000575241.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244604 AF XY: 0.00000753

Gnomad AFR exome AF: 0.0000668

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 AF: 0.00000206 AC: 3 AN: 1457544 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 724966

African (AFR) AF: 0.0000605 AC: 2 AN: 33060

American (AMR) AF: 0.00 AC: 0 AN: 44300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26026

East Asian (EAS) AF: 0.00 AC: 0 AN: 39420

South Asian (SAS) AF: 0.00 AC: 0 AN: 85194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110694

Other (OTH) AF: 0.0000166 AC: 1 AN: 60242

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.25
DANN	Benign	0.74
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0083	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.14
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.0060
Sift	Benign	0.36	T
Sift4G	Benign	0.34	T
Polyphen		0.0010	B
Vest4		0.074
MutPred		0.19		Loss of catalytic residue at V437 (P = 0.077)
MVP		0.12
MPC		0.16
ClinPred		0.085	T
GERP RS		-1.8
Varity_R		0.033
gMVP		0.075
Mutation Taster		=98/2	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

dbSNP: rs755684879; hg19: chr19-4523623;