NM_001122.4:c.751T>C

Variant names:

• chr9-19119676-A-G
• rs35568725
• NM_001122.4:c.751T>C

Variant summary

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

The NM_001122.4(PLIN2):​c.751T>C​(p.Ser251Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0485 in 1,603,904 control chromosomes in the GnomAD database, including 2,159 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 0.040 (180 hom., cov: 32)
  • Exomes 𝑓: 0.049 (1979 hom.)
• Consequence: PLIN2 NM_001122.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• Publications: 43 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040703714).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN2	NM_001122.4	c.751T>C	p.Ser251Pro	missense_variant	Exon 6 of 8	ENST00000276914.7	NP_001113.2
PLIN2	XM_017014259.3	c.751T>C	p.Ser251Pro	missense_variant	Exon 6 of 9		XP_016869748.1
PLIN2	NR_038064.2	n.934T>C		non_coding_transcript_exon_variant	Exon 5 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN2	ENST00000276914.7	c.751T>C	p.Ser251Pro	missense_variant	Exon 6 of 8	1	NM_001122.4	ENSP00000276914.2

Frequencies

GnomAD3 genomes AF: 0.0399 AC: 6076 AN: 152160 Hom.: 180 Cov.: 32

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0260

Gnomad ASJ AF: 0.0260

Gnomad EAS AF: 0.00693

Gnomad SAS AF: 0.0326

Gnomad FIN AF: 0.0830

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0568

Gnomad OTH AF: 0.0450

GnomAD2 exomes AF: 0.0406 AC: 10116 AN: 248940 AF XY: 0.0418

Gnomad AFR exome AF: 0.0123

Gnomad AMR exome AF: 0.0190

Gnomad ASJ exome AF: 0.0246

Gnomad EAS exome AF: 0.00615

Gnomad FIN exome AF: 0.0825

Gnomad NFE exome AF: 0.0522

Gnomad OTH exome AF: 0.0438

GnomAD4 exome AF: 0.0494 AC: 71739 AN: 1451626 Hom.: 1979 Cov.: 30 AF XY: 0.0491 AC XY: 35379 AN XY: 721166

African (AFR) AF: 0.0105 AC: 350 AN: 33202

American (AMR) AF: 0.0204 AC: 896 AN: 43838

Ashkenazi Jewish (ASJ) AF: 0.0243 AC: 631 AN: 25940

East Asian (EAS) AF: 0.0123 AC: 486 AN: 39558

South Asian (SAS) AF: 0.0312 AC: 2666 AN: 85386

European-Finnish (FIN) AF: 0.0825 AC: 4393 AN: 53240

Middle Eastern (MID) AF: 0.0146 AC: 71 AN: 4860

European-Non Finnish (NFE) AF: 0.0537 AC: 59393 AN: 1105778

Other (OTH) AF: 0.0477 AC: 2853 AN: 59824

GnomAD4 genome AF: 0.0399 AC: 6076 AN: 152278 Hom.: 180 Cov.: 32 AF XY: 0.0413 AC XY: 3076 AN XY: 74450

African (AFR) AF: 0.0125 AC: 518 AN: 41576

American (AMR) AF: 0.0260 AC: 397 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0260 AC: 90 AN: 3468

East Asian (EAS) AF: 0.00694 AC: 36 AN: 5186

South Asian (SAS) AF: 0.0326 AC: 157 AN: 4816

European-Finnish (FIN) AF: 0.0830 AC: 880 AN: 10608

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0568 AC: 3862 AN: 68026

Other (OTH) AF: 0.0445 AC: 94 AN: 2112

Alfa AF: 0.0467 Hom.: 492

Bravo AF: 0.0350

TwinsUK AF: 0.0472 AC: 175

ALSPAC AF: 0.0519 AC: 200

ESP6500AA AF: 0.0143 AC: 63

ESP6500EA AF: 0.0547 AC: 470

ExAC AF: 0.0406 AC: 4935

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.054
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.2
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.12
Sift	Benign	0.065	T
Sift4G	Benign	0.099	T
Polyphen		0.11	B
Vest4		0.32
MPC		0.053
ClinPred		0.041	T
GERP RS		4.8
Varity_R		0.55
gMVP		0.71
Mutation Taster		=82/18	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: rs35568725; hg19: chr9-19119674; COSMIC: COSV52804582; COSMIC: COSV52804582;