NM_001367868.2:c.2242A>C

Variant names:

• chr19-4511718-T-G
• rs62115190
• NM_001367868.2:c.2242A>C

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.2242A>C​(p.Ile748Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I748V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 10)
• Consequence: PLIN4 NM_001367868.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 17 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=0.08976796).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN4	NM_001367868.2	MANE Select	c.2242A>C	p.Ile748Leu	missense	Exon 5 of 8	NP_001354797.1	Q96Q06
	PLIN4	NM_001393888.1		c.2245A>C	p.Ile749Leu	missense	Exon 5 of 8	NP_001380817.1	A0A0J9YXN7
	PLIN4	NM_001393889.1		c.2245A>C	p.Ile749Leu	missense	Exon 5 of 8	NP_001380818.1	A0A0J9YXN7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN4	ENST00000301286.5	TSL:5 MANE Select	c.2242A>C	p.Ile748Leu	missense	Exon 5 of 8	ENSP00000301286.4	Q96Q06
	PLIN4	ENST00000966625.1		c.2428A>C	p.Ile810Leu	missense	Exon 6 of 9	ENSP00000636684.1
	PLIN4	ENST00000966622.1		c.2425A>C	p.Ile809Leu	missense	Exon 6 of 9	ENSP00000636681.1

Frequencies

GnomAD3 genomes Cov.: 10

GnomAD4 exome Cov.: 70

GnomAD4 genome Cov.: 10

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.96
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.030
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.11
Sift	Benign	0.17	T
Sift4G	Benign	0.19	T
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.44		Loss of catalytic residue at I734 (P = 0.0246)
MVP		0.030
ClinPred		0.12	T
GERP RS		4.6
Varity_R		0.078
gMVP		0.020
Mutation Taster		=99/1	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: rs62115190; hg19: chr19-4511730;