chr12-14507007-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024829.6(PLBD1):​c.1298G>A​(p.Arg433Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,613,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

PLBD1
NM_024829.6 missense

Scores

12
4
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.38
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.859

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLBD1NM_024829.6 linkc.1298G>A p.Arg433Gln missense_variant Exon 9 of 11 ENST00000240617.10 NP_079105.4 Q6P4A8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLBD1ENST00000240617.10 linkc.1298G>A p.Arg433Gln missense_variant Exon 9 of 11 1 NM_024829.6 ENSP00000240617.5 Q6P4A8

Frequencies

GnomAD3 genomes
AF:
0.0000724
AC:
11
AN:
151992
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000189
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000438
AC:
11
AN:
251336
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135832
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000704
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000623
AC:
91
AN:
1461810
Hom.:
0
Cov.:
30
AF XY:
0.0000578
AC XY:
42
AN XY:
727208
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000764
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000724
AC:
11
AN:
151992
Hom.:
0
Cov.:
33
AF XY:
0.0000808
AC XY:
6
AN XY:
74218
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000189
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000900
Hom.:
0
Bravo
AF:
0.0000604
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000412
AC:
5
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 15, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1298G>A (p.R433Q) alteration is located in exon 9 (coding exon 9) of the PLBD1 gene. This alteration results from a G to A substitution at nucleotide position 1298, causing the arginine (R) at amino acid position 433 to be replaced by a glutamine (Q). 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
0.87
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Pathogenic
0.20
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.10
T
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.95
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.86
D
MetaSVM
Uncertain
-0.0016
T
MutationAssessor
Pathogenic
4.2
H
PrimateAI
Benign
0.43
T
PROVEAN
Uncertain
-4.0
D
REVEL
Uncertain
0.49
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.92
MVP
0.41
MPC
0.84
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.83
gMVP
0.93

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.

Other links and lift over

dbSNP: rs376366615; hg19: chr12-14659941; COSMIC: COSV53694665; COSMIC: COSV53694665; API