rs262562

Variant names:

• chr19-4864464-T-G
• rs262562
• NM_005817.5:c.-17-3053A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005817.5(PLIN3):​c.-17-3053A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 146,092 control chromosomes in the GnomAD database, including 14,001 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (14001 hom., cov: 21)
• Consequence: PLIN3 NM_005817.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.76
• Publications: 2 publications found

Genes affected

PLIN3 (HGNC:16893): (perilipin 3) Mannose 6-phophate receptors (MPRs) deliver lysosomal hydrolase from the Golgi to endosomes and then return to the Golgi complex. The protein encoded by this gene interacts with the cytoplasmic domains of both cation-independent and cation-dependent MPRs, and is required for endosome-to-Golgi transport. This protein also binds directly to the GTPase RAB9 (RAB9A), a member of the RAS oncogene family. The interaction with RAB9 has been shown to increase the affinity of this protein for its cargo. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN3	NM_005817.5	c.-17-3053A>C		intron_variant	Intron 1 of 7	ENST00000221957.9	NP_005808.3
PLIN3	NM_001164189.2	c.-17-3053A>C		intron_variant	Intron 1 of 7		NP_001157661.1
PLIN3	NM_001164194.2	c.-17-3053A>C		intron_variant	Intron 1 of 7		NP_001157666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN3	ENST00000221957.9	c.-17-3053A>C		intron_variant	Intron 1 of 7	1	NM_005817.5	ENSP00000221957.3

Frequencies

GnomAD3 genomes AF: 0.432 AC: 63014 AN: 145994 Hom.: 13987 Cov.: 21

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.432

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.432 AC: 63062 AN: 146092 Hom.: 14001 Cov.: 21 AF XY: 0.427 AC XY: 30258 AN XY: 70814

African (AFR) AF: 0.537 AC: 21131 AN: 39340

American (AMR) AF: 0.381 AC: 5536 AN: 14528

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1435 AN: 3438

East Asian (EAS) AF: 0.428 AC: 2144 AN: 5012

South Asian (SAS) AF: 0.476 AC: 2151 AN: 4522

European-Finnish (FIN) AF: 0.344 AC: 3258 AN: 9482

Middle Eastern (MID) AF: 0.400 AC: 112 AN: 280

European-Non Finnish (NFE) AF: 0.390 AC: 25977 AN: 66604

Other (OTH) AF: 0.432 AC: 861 AN: 1994

Alfa AF: 0.416 Hom.: 962

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.65
DANN	Benign	0.15
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs262562; hg19: chr19-4864476;