chr19-4504656-G-A

Position:

• chr19-4504656-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367868.2(PLIN4):​c.3919C>T​(p.His1307Tyr) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLIN4 NM_001367868.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11931619).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLIN4	NM_001367868.2	c.3919C>T	p.His1307Tyr	missense_variant	8/8	ENST00000301286.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLIN4	ENST00000301286.5	c.3919C>T	p.His1307Tyr	missense_variant	8/8	5	NM_001367868.2	P1
PLIN4	ENST00000633942.1	c.3922C>T	p.His1308Tyr	missense_variant	8/8	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2024

The c.3877C>T (p.H1293Y) alteration is located in exon 6 (coding exon 6) of the PLIN4 gene. This alteration results from a C to T substitution at nucleotide position 3877, causing the histidine (H) at amino acid position 1293 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.022	T;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.7	D;.
REVEL	Benign	0.029
Sift	Benign	0.086	T;.
Sift4G	Benign	0.29	T;T
Polyphen		0.15	B;.
Vest4		0.25
MutPred		0.41		Loss of catalytic residue at L1295 (P = 0.046);.;
MVP		0.048
ClinPred		0.22	T
GERP RS		2.1
Varity_R		0.16
gMVP		0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs1976032459; hg19: chr19-4504668;