Genetic Variant PLBD1:p.Leu25Gln (chr12-14567623-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024829.6(PLBD1):c.74T>A(p.Leu25Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00065 ( 0 hom. )

Consequence

PLBD1
NM_024829.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.579

Variant links:

Genes affected

PLBD1 (HGNC:26215): (phospholipase B domain containing 1) Predicted to enable phospholipase activity. Predicted to be involved in phospholipid catabolic process. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

PLBD1 links:

PLBD1-AS1 (HGNC:51143): (PLBD1 antisense RNA 1)

PLBD1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002184689).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLBD1	NM_024829.6 link	c.74T>A	p.Leu25Gln	missense_variant	Exon 1 of 11	ENST00000240617.10	NP_079105.4	Q6P4A8
PLBD1-AS1	NR_120465.1 link	n.-109A>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLBD1	ENST00000240617.10 link	c.74T>A	p.Leu25Gln	missense_variant	Exon 1 of 11	1	NM_024829.6	ENSP00000240617.5		Q6P4A8

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

18628

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:

0.000280

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000777

AC:

AN:

56624

Hom.:

AF XY:

0.000786

AC XY:

AN XY:

33078

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00118

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00180

Gnomad SAS exome

AF:

0.000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000988

Gnomad OTH exome

AF:

0.00171

GnomAD4 exome

AF:

0.000645

AC:

101

AN:

156522

Hom.:

Cov.:

AF XY:

0.000770

AC XY:

AN XY:

74070

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00906

Gnomad4 ASJ exome

AF:

0.00117

Gnomad4 EAS exome

AF:

0.00209

Gnomad4 SAS exome

AF:

0.00349

Gnomad4 FIN exome

AF:

0.000593

Gnomad4 NFE exome

AF:

0.000395

Gnomad4 OTH exome

AF:

0.000856

GnomAD4 genome

AF:

0.000107

AC:

AN:

18628

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

9106

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:

0.000280

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.141

AC:

727

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.9

DANN

Benign

0.76

DEOGEN2

Benign

0.0035

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.21

MetaRNN

Benign

0.0022

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.41

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.49

REVEL

Benign

0.037

Sift

Benign

0.059

Sift4G

Benign

0.094

Polyphen

0.0030

Vest4

0.11

MutPred

0.51

Gain of sheet (P = 0.0344);

MPC

0.21

ClinPred

0.0099

GERP RS

-2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.077

gMVP

0.61

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over