chr2-28532149-C-A

Variant names:

Variant summary

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

The NM_153021.5(PLB1):c.510C>A(p.Phe170Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

PLB1
NM_153021.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.433

Variant links:

Genes affected

PLB1 (HGNC:30041): (phospholipase B1) This gene encodes a membrane-associated phospholipase that displays lysophospholipase and phospholipase A2 activities through removal of sn-1 and sn-2 fatty acids of glycerophospholipids. In addition, it displays lipase and retinyl ester hydrolase activities. The encoded protein is highly conserved and is composed of a large, glycosylated extracellular domain composed of four tandem homologous domains, followed by a hydrophobic segment that anchors the enzyme to the membrane and a short C-terminal cytoplasmic tail. This gene has been identified as a candidate rheumatoid arthritis risk gene. [provided by RefSeq, Jul 2016]

PLB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLB1	NM_153021.5 link	c.510C>A	p.Phe170Leu	missense_variant	Exon 9 of 58	ENST00000327757.10	NP_694566.4	Q6P1J6-1B2RWP8
PLB1	NM_001170585.2 link	c.510C>A	p.Phe170Leu	missense_variant	Exon 9 of 57		NP_001164056.1	Q6P1J6-3B2RWP8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLB1	ENST00000327757.10 link	c.510C>A	p.Phe170Leu	missense_variant	Exon 9 of 58	1	NM_153021.5	ENSP00000330442.5	Q6P1J6-1
PLB1	ENST00000422425.6 link	c.510C>A	p.Phe170Leu	missense_variant	Exon 9 of 57	1		ENSP00000416440.2	Q6P1J6-3
PLB1	ENST00000404858.5 link	c.504C>A	p.Phe168Leu	missense_variant	Exon 9 of 57	1		ENSP00000384187.1	H7BYX7
PLB1	ENST00000416713.5 link	c.342C>A	p.Phe114Leu	missense_variant	Exon 9 of 11	5		ENSP00000407076.1	C9JYQ2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250238

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135264

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1460848

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726742

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.510C>A (p.F170L) alteration is located in exon 9 (coding exon 9) of the PLB1 gene. This alteration results from a C to A substitution at nucleotide position 510, causing the phenylalanine (F) at amino acid position 170 to be replaced by a leucine (L). 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

Pathogenic

0.92

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

.;T;.

Eigen

Benign

-0.030

Eigen_PC

Benign

-0.000085

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.61

T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.2

.;M;M

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-5.2

D;N;N

REVEL

Benign

0.18

Sift

Benign

0.18

T;T;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.019, 0.41

.;B;B

Vest4

0.49, 0.58

MutPred

0.54

.;Loss of catalytic residue at F170 (P = 0.0084);Loss of catalytic residue at F170 (P = 0.0084);

MVP

0.26

MPC

0.048

ClinPred

0.95

GERP RS

4.2

Varity_R

0.11

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: -41

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over