chr19-4523919-C-T

Variant names:

• chr19-4523919-C-T
• rs377657199
• NM_001013706.3:c.1001G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001013706.3(PLIN5):​c.1001G>A​(p.Arg334His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,526,900 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R334C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: PLIN5 NM_001013706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.339
• Publications: 1 publications found

Genes affected

PLIN5 (HGNC:33196): (perilipin 5) Predicted to enable identical protein binding activity and lipase binding activity. Predicted to be involved in several processes, including negative regulation of peroxisome proliferator activated receptor signaling pathway; regulation of lipase activity; and regulation of lipid metabolic process. Located in intracellular membrane-bounded organelle and lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017984748).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013706.3. 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
	PLIN5	NM_001013706.3	MANE Select	c.1001G>A	p.Arg334His	missense	Exon 8 of 8	NP_001013728.2	Q00G26

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN5	ENST00000381848.7	TSL:1 MANE Select	c.1001G>A	p.Arg334His	missense	Exon 8 of 8	ENSP00000371272.2	Q00G26
	PLIN5	ENST00000905186.1		c.1238G>A	p.Arg413His	missense	Exon 9 of 9	ENSP00000575245.1
	PLIN5	ENST00000905182.1		c.1202G>A	p.Arg401His	missense	Exon 9 of 9	ENSP00000575241.1

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0000654

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: 0.00

GnomAD2 exomes AF: 0.0000732 AC: 9 AN: 122920 AF XY: 0.0000876

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000135

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000120

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000119 AC: 164 AN: 1374702 Hom.: 1 Cov.: 30 AF XY: 0.000118 AC XY: 80 AN XY: 678964

African (AFR) AF: 0.0000341 AC: 1 AN: 29364

American (AMR) AF: 0.000118 AC: 4 AN: 33950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24414

East Asian (EAS) AF: 0.00 AC: 0 AN: 34534

South Asian (SAS) AF: 0.00 AC: 0 AN: 77888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5492

European-Non Finnish (NFE) AF: 0.000136 AC: 147 AN: 1077836

Other (OTH) AF: 0.000209 AC: 12 AN: 57390

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74348

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000870 Hom.: 0

Bravo AF: 0.000185

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000264 AC: 2

ExAC AF: 0.0000399 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	16
DANN	Benign	0.82
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.41	N
PhyloP100		-0.34
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.52	N
REVEL	Benign	0.031
Sift	Benign	0.74	T
Sift4G	Benign	0.63	T
Polyphen		0.0030	B
Vest4		0.11
MVP		0.040
MPC		0.26
ClinPred		0.022	T
GERP RS		1.7
Varity_R		0.022
gMVP		0.21
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs377657199; hg19: chr19-4523931;