rs202096657

Variant names:

• chr19-4504689-C-G
• rs202096657
• NM_001367868.2:c.3886G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-4504689-C-G
• chr19-4504689-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001367868.2(PLIN4):​c.3886G>C​(p.Ala1296Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,600,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: PLIN4 NM_001367868.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.31
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04116285).
• BS2: High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN4	NM_001367868.2	c.3886G>C	p.Ala1296Pro	missense_variant	Exon 8 of 8	ENST00000301286.5	NP_001354797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN4	ENST00000301286.5	c.3886G>C	p.Ala1296Pro	missense_variant	Exon 8 of 8	5	NM_001367868.2	ENSP00000301286.4
PLIN4	ENST00000633942.1	c.3889G>C	p.Ala1297Pro	missense_variant	Exon 8 of 8	5		ENSP00000488481.1

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.0000810 AC: 18 AN: 222132 AF XY: 0.0000568

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000302

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.000179

GnomAD4 exome AF: 0.000232 AC: 336 AN: 1448604 Hom.: 0 Cov.: 31 AF XY: 0.000204 AC XY: 147 AN XY: 720544

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.000114 AC: 5 AN: 43966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25936

East Asian (EAS) AF: 0.00 AC: 0 AN: 39456

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.000281 AC: 312 AN: 1109724

Other (OTH) AF: 0.000300 AC: 18 AN: 60004

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12 AN XY: 74492

African (AFR) AF: 0.0000481 AC: 2 AN: 41586

American (AMR) AF: 0.000784 AC: 12 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68014

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000175 Hom.: 0

Bravo AF: 0.000283

ExAC AF: 0.0000504 AC: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3844G>C (p.A1282P) alteration is located in exon 6 (coding exon 6) of the PLIN4 gene. This alteration results from a G to C substitution at nucleotide position 3844, causing the alanine (A) at amino acid position 1282 to be replaced by a proline (P). 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	0.090
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.1
DANN	Benign	0.96
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L;.
PhyloP100		-1.3
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.0	N;.
REVEL	Benign	0.018
Sift	Benign	0.31	T;.
Sift4G	Benign	0.37	T;T
Polyphen		0.058	B;.
Vest4		0.13
MVP		0.030
ClinPred		0.070	T
GERP RS		-5.1
Varity_R		0.26
gMVP		0.23
Mutation Taster		=96/4	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: rs202096657; hg19: chr19-4504701;