Variant chr12-14567684-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024829.6(PLBD1):c.13G>T(p.Gly5Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,462,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

PLBD1
NM_024829.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.47

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044322163).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLBD1	NM_024829.6 link	c.13G>T	p.Gly5Cys	missense_variant	Exon 1 of 11	ENST00000240617.10	NP_079105.4	Q6P4A8
PLBD1-AS1	NR_120465.1 link	n.-48C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLBD1	ENST00000240617.10 link	c.13G>T	p.Gly5Cys	missense_variant	Exon 1 of 11	1	NM_024829.6	ENSP00000240617.5		Q6P4A8

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000134

AC:

AN:

52116

Hom.:

AF XY:

0.000165

AC XY:

AN XY:

30338

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:

0.000366

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000253

AC:

331

AN:

1310620

Hom.:

Cov.:

AF XY:

0.000236

AC XY:

152

AN XY:

644898

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000190

Gnomad4 NFE exome

AF:

0.000305

Gnomad4 OTH exome

AF:

0.0000920

GnomAD4 genome

AF:

0.000105

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000121

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:

0.000162

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000945

ExAC

AF:

0.0000537

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.13G>T (p.G5C) alteration is located in exon 1 (coding exon 1) of the PLBD1 gene. This alteration results from a G to T substitution at nucleotide position 13, causing the glycine (G) at amino acid position 5 to be replaced by a cysteine (C). 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

0.15

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.1

DANN

Benign

0.92

DEOGEN2

Benign

0.00088

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.33

M_CAP

Benign

0.0052

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.31

REVEL

Benign

0.020

Sift

Pathogenic

0.0

Sift4G

Benign

0.077

Polyphen

0.0020

Vest4

0.16

MVP

0.030

MPC

0.21

ClinPred

0.050

GERP RS

-6.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.19

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over