chr12-14506941-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_024829.6(PLBD1):​c.1364G>A​(p.Arg455Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,613,618 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 0.000092 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

PLBD1
NM_024829.6 missense

Scores

9
5
5

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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.837

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLBD1NM_024829.6 linkuse as main transcriptc.1364G>A p.Arg455Gln missense_variant 9/11 ENST00000240617.10 NP_079105.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLBD1ENST00000240617.10 linkuse as main transcriptc.1364G>A p.Arg455Gln missense_variant 9/111 NM_024829.6 ENSP00000240617 P1

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152142
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.0000441
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000996
AC:
25
AN:
251108
Hom.:
0
AF XY:
0.0000884
AC XY:
12
AN XY:
135716
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.0000463
Gnomad NFE exome
AF:
0.0000617
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000527
AC:
77
AN:
1461476
Hom.:
0
Cov.:
30
AF XY:
0.0000564
AC XY:
41
AN XY:
727014
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.0000405
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152142
Hom.:
0
Cov.:
33
AF XY:
0.000121
AC XY:
9
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.000106
Hom.:
0
Bravo
AF:
0.0000982
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.000123
AC:
15
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000164
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 22, 2022The c.1364G>A (p.R455Q) 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 1364, causing the arginine (R) at amino acid position 455 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
Uncertain
0.40
BayesDel_addAF
Uncertain
0.058
T
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.077
T
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.069
D
MetaRNN
Pathogenic
0.84
D
MetaSVM
Benign
-0.36
T
MutationAssessor
Pathogenic
3.0
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.49
T
PROVEAN
Uncertain
-3.5
D
REVEL
Uncertain
0.55
Sift
Benign
0.091
T
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.94
MVP
0.36
MPC
0.84
ClinPred
0.73
D
GERP RS
5.1
Varity_R
0.53
gMVP
0.91

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs532368691; hg19: chr12-14659875; API