rs9973235

Variant names:

• chr19-4847701-A-G
• rs9973235
• NM_005817.5:c.824T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-4847701-A-G
• chr19-4847701-A-T

Variant summary

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

The NM_005817.5(PLIN3):​c.824T>C​(p.Val275Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 1,599,220 control chromosomes in the GnomAD database, including 592,895 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.88 (58651 hom., cov: 32)
  • Exomes 𝑓: 0.86 (534244 hom.)
• Consequence: PLIN3 NM_005817.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46
• Publications: 33 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 (MetaRNN=1.7516448E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN3	NM_005817.5	c.824T>C	p.Val275Ala	missense_variant	Exon 6 of 8	ENST00000221957.9	NP_005808.3
PLIN3	NM_001164189.2	c.824T>C	p.Val275Ala	missense_variant	Exon 6 of 8		NP_001157661.1
PLIN3	NM_001164194.2	c.788T>C	p.Val263Ala	missense_variant	Exon 6 of 8		NP_001157666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN3	ENST00000221957.9	c.824T>C	p.Val275Ala	missense_variant	Exon 6 of 8	1	NM_005817.5	ENSP00000221957.3
PLIN3	ENST00000585479.5	c.824T>C	p.Val275Ala	missense_variant	Exon 6 of 8	1		ENSP00000465596.1
PLIN3	ENST00000592528.5	c.788T>C	p.Val263Ala	missense_variant	Exon 6 of 8	2		ENSP00000467803.1
PLIN3	ENST00000589163.5	c.405+116T>C		intron_variant	Intron 3 of 4	3		ENSP00000468476.1

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133433 AN: 152036 Hom.: 58603 Cov.: 32

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.898

GnomAD2 exomes AF: 0.871 AC: 198297 AN: 227610 AF XY: 0.867

Gnomad AFR exome AF: 0.905

Gnomad AMR exome AF: 0.940

Gnomad ASJ exome AF: 0.859

Gnomad EAS exome AF: 0.907

Gnomad FIN exome AF: 0.857

Gnomad NFE exome AF: 0.849

Gnomad OTH exome AF: 0.875

GnomAD4 exome AF: 0.859 AC: 1242947 AN: 1447066 Hom.: 534244 Cov.: 42 AF XY: 0.859 AC XY: 617528 AN XY: 718910

African (AFR) AF: 0.907 AC: 30017 AN: 33104

American (AMR) AF: 0.937 AC: 39926 AN: 42598

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 22217 AN: 25758

East Asian (EAS) AF: 0.876 AC: 34257 AN: 39088

South Asian (SAS) AF: 0.856 AC: 72208 AN: 84346

European-Finnish (FIN) AF: 0.861 AC: 44896 AN: 52152

Middle Eastern (MID) AF: 0.920 AC: 4571 AN: 4966

European-Non Finnish (NFE) AF: 0.853 AC: 942834 AN: 1105326

Other (OTH) AF: 0.871 AC: 52021 AN: 59728

GnomAD4 genome AF: 0.878 AC: 133537 AN: 152154 Hom.: 58651 Cov.: 32 AF XY: 0.880 AC XY: 65426 AN XY: 74382

African (AFR) AF: 0.906 AC: 37630 AN: 41522

American (AMR) AF: 0.918 AC: 14005 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2978 AN: 3472

East Asian (EAS) AF: 0.900 AC: 4642 AN: 5156

South Asian (SAS) AF: 0.866 AC: 4176 AN: 4820

European-Finnish (FIN) AF: 0.864 AC: 9165 AN: 10604

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.855 AC: 58142 AN: 68006

Other (OTH) AF: 0.894 AC: 1888 AN: 2112

Alfa AF: 0.864 Hom.: 259808

Bravo AF: 0.885

TwinsUK AF: 0.852 AC: 3159

ALSPAC AF: 0.847 AC: 3264

ESP6500AA AF: 0.914 AC: 4014

ESP6500EA AF: 0.853 AC: 7331

ExAC AF: 0.863 AC: 104325

Asia WGS AF: 0.852 AC: 2964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	17
DANN	Benign	0.88
DEOGEN2	Benign	0.051	T;.;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.15	T;T;T
MetaRNN	Benign	0.0000018	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.4	N;.;N
PhyloP100		3.5
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.22	N;.;.
REVEL	Benign	0.13
Sift	Benign	0.51	T;.;.
Sift4G	Benign	0.42	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.031
MPC		0.12
ClinPred		0.0065	T
GERP RS		2.2
Varity_R		0.015
gMVP		0.081
Mutation Taster		=77/23	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: rs9973235; hg19: chr19-4847713; COSMIC: COSV107288951; COSMIC: COSV107288951;