chr19-4511943-T-A

Variant names:

• chr19-4511943-T-A
• rs7260518
• NM_001367868.2:c.2017A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367868.2(PLIN4):​c.2017A>T​(p.Ser673Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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: not found (cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLIN4 NM_001367868.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 27 publications found

Genes affected

PLIN4 (HGNC:29393): (perilipin 4) Members of the perilipin family, such as PLIN4, coat intracellular lipid storage droplets (Wolins et al., 2003 [PubMed 12840023]).[supplied by OMIM, Feb 2010]

PLIN4 Gene-Disease associations (from GenCC):

• vacuolar Neuromyopathy

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19663635).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367868.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN4	NM_001367868.2	MANE Select	c.2017A>T	p.Ser673Cys	missense	Exon 5 of 8	NP_001354797.1
	PLIN4	NM_001393888.1		c.2020A>T	p.Ser674Cys	missense	Exon 5 of 8	NP_001380817.1
	PLIN4	NM_001393889.1		c.2020A>T	p.Ser674Cys	missense	Exon 5 of 8	NP_001380818.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN4	ENST00000301286.5	TSL:5 MANE Select	c.2017A>T	p.Ser673Cys	missense	Exon 5 of 8	ENSP00000301286.4
	PLIN4	ENST00000633942.1	TSL:5	c.2020A>T	p.Ser674Cys	missense	Exon 5 of 8	ENSP00000488481.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1360466 Hom.: 0 Cov.: 104 AF XY: 0.00 AC XY: 0 AN XY: 673070

African (AFR) AF: 0.00 AC: 0 AN: 32234

American (AMR) AF: 0.00 AC: 0 AN: 40576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23128

East Asian (EAS) AF: 0.00 AC: 0 AN: 29714

South Asian (SAS) AF: 0.00 AC: 0 AN: 72770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5336

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1055088

Other (OTH) AF: 0.00 AC: 0 AN: 54664

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.15
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.13
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.91	P
Vest4		0.30
MutPred		0.47		Gain of sheet (P = 0.0149)
MVP		0.048
ClinPred		0.38	T
GERP RS		3.7
Varity_R		0.075
gMVP		0.020
Mutation Taster		=97/3	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: rs7260518; hg19: chr19-4511955;