12-14506941-C-T
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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
NM_024829.6 missense
Scores
9
5
5
Clinical Significance
Conservation
PhyloP100: 7.38
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]
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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 |
---|---|---|---|---|---|---|---|---|
PLBD1 | NM_024829.6 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
PLBD1 | ENST00000240617.10 | c.1364G>A | p.Arg455Gln | missense_variant | 9/11 | 1 | NM_024829.6 | ENSP00000240617 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152142Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000996 AC: 25AN: 251108Hom.: 0 AF XY: 0.0000884 AC XY: 12AN XY: 135716
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GnomAD4 exome AF: 0.0000527 AC: 77AN: 1461476Hom.: 0 Cov.: 30 AF XY: 0.0000564 AC XY: 41AN XY: 727014
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GnomAD4 genome AF: 0.0000920 AC: 14AN: 152142Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74330
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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 submitter | clinical testing | Ambry Genetics | Mar 22, 2022 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at