NM_001013706.3:c.1042C>T

Variant names:

• chr19-4523878-G-A
• rs752949459
• NM_001013706.3:c.1042C>T

Variant summary

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

The NM_001013706.3(PLIN5):​c.1042C>T​(p.Arg348Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000056 in 1,518,734 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000061 (0 hom.)
• Consequence: PLIN5 NM_001013706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.84
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1042C>T	p.Arg348Trp	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.1042C>T	p.Arg348Trp	missense	Exon 8 of 8	ENSP00000371272.2	Q00G26
	PLIN5	ENST00000905186.1		c.1279C>T	p.Arg427Trp	missense	Exon 9 of 9	ENSP00000575245.1
	PLIN5	ENST00000905182.1		c.1243C>T	p.Arg415Trp	missense	Exon 9 of 9	ENSP00000575241.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000845 AC: 1 AN: 118342 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

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: 0.000302

GnomAD4 exome AF: 0.0000615 AC: 84 AN: 1366550 Hom.: 0 Cov.: 30 AF XY: 0.0000563 AC XY: 38 AN XY: 675308

African (AFR) AF: 0.0000348 AC: 1 AN: 28774

American (AMR) AF: 0.0000323 AC: 1 AN: 30974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22772

East Asian (EAS) AF: 0.00 AC: 0 AN: 35144

South Asian (SAS) AF: 0.00 AC: 0 AN: 75178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34070

Middle Eastern (MID) AF: 0.000186 AC: 1 AN: 5380

European-Non Finnish (NFE) AF: 0.0000733 AC: 79 AN: 1077360

Other (OTH) AF: 0.0000352 AC: 2 AN: 56898

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000141 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.00000953 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		1.8
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.42
MVP		0.73
MPC		0.77
ClinPred		0.92	D
GERP RS		3.5
Varity_R		0.49
gMVP		0.50
Mutation Taster		=65/35	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: rs752949459; hg19: chr19-4523890;