chr19-4851096-G-T

Position:

• chr19-4851096-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005817.5(PLIN3):​c.634+920C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 151,864 control chromosomes in the GnomAD database, including 28,190 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 0.61 (28190 hom., cov: 32)
• Consequence: PLIN3 NM_005817.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.34

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLIN3	NM_005817.5	c.634+920C>A		intron_variant		ENST00000221957.9	NP_005808.3
PLIN3	NM_001164189.2	c.634+920C>A		intron_variant			NP_001157661.1
PLIN3	NM_001164194.2	c.598+920C>A		intron_variant			NP_001157666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLIN3	ENST00000221957.9	c.634+920C>A		intron_variant		1	NM_005817.5	ENSP00000221957.3
PLIN3	ENST00000585479.5	c.634+920C>A		intron_variant		1		ENSP00000465596.1
PLIN3	ENST00000592528.5	c.598+920C>A		intron_variant		2		ENSP00000467803.1
PLIN3	ENST00000589163.5	c.331+920C>A		intron_variant		3		ENSP00000468476.1

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92084 AN: 151746 Hom.: 28196 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.607 AC: 92110 AN: 151864 Hom.: 28190 Cov.: 32 AF XY: 0.598 AC XY: 44354 AN XY: 74220

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.604

Alfa AF: 0.617 Hom.: 3623

Bravo AF: 0.620

Asia WGS AF: 0.516 AC: 1796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.42
DANN	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs12979855; hg19: chr19-4851108;