chr9-19116397-T-C

Variant names:

• chr9-19116397-T-C
• NM_001122.4:c.1165A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001122.4(PLIN2):​c.1165A>G​(p.Met389Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PLIN2 NM_001122.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05
• Publications: 0 publications found

Genes affected

PLIN2 (HGNC:248): (perilipin 2) The protein encoded by this gene belongs to the perilipin family, members of which coat intracellular lipid storage droplets. This protein is associated with the lipid globule surface membrane material, and maybe involved in development and maintenance of adipose tissue. However, it is not restricted to adipocytes as previously thought, but is found in a wide range of cultured cell lines, including fibroblasts, endothelial and epithelial cells, and tissues, such as lactating mammary gland, adrenal cortex, Sertoli and Leydig cells, and hepatocytes in alcoholic liver cirrhosis, suggesting that it may serve as a marker of lipid accumulation in diverse cell types and diseases. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.745

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122.4. 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
	PLIN2	NM_001122.4	MANE Select	c.1165A>G	p.Met389Val	missense	Exon 8 of 8	NP_001113.2
	PLIN2	NR_038064.2		n.1348A>G		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN2	ENST00000276914.7	TSL:1 MANE Select	c.1165A>G	p.Met389Val	missense	Exon 8 of 8	ENSP00000276914.2	Q99541
	PLIN2	ENST00000957811.1		c.1192A>G	p.Met398Val	missense	Exon 8 of 8	ENSP00000627870.1
	PLIN2	ENST00000907780.1		c.1165A>G	p.Met389Val	missense	Exon 10 of 10	ENSP00000577839.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112002

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome Cov.: 32

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	0.14
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0081	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.25
Sift	Benign	0.63	T
Sift4G	Benign	0.48	T
Polyphen		1.0	D
Vest4		0.74
MutPred		0.52		Loss of disorder (P = 0.1185)
MVP		0.59
MPC		0.053
ClinPred		0.57	D
GERP RS		5.5
Varity_R		0.16
gMVP		0.58
Mutation Taster		=85/15	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

hg19: chr9-19116395;