chr12-14511699-G-C

Variant summary

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

The NM_024829.6(PLBD1):ā€‹c.857C>Gā€‹(p.Ser286Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,613,884 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00013 ( 0 hom., cov: 32)
Exomes š‘“: 0.00010 ( 1 hom. )

Consequence

PLBD1
NM_024829.6 missense

Scores

11
5
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.27
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, 0.848

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLBD1NM_024829.6 linkuse as main transcriptc.857C>G p.Ser286Cys missense_variant 7/11 ENST00000240617.10 NP_079105.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLBD1ENST00000240617.10 linkuse as main transcriptc.857C>G p.Ser286Cys missense_variant 7/111 NM_024829.6 ENSP00000240617 P1
PLBD1ENST00000541800.6 linkuse as main transcriptn.480C>G non_coding_transcript_exon_variant 2/33
PLBD1ENST00000541618.1 linkuse as main transcriptc.*514C>G 3_prime_UTR_variant, NMD_transcript_variant 6/65 ENSP00000441278

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152108
Hom.:
0
Cov.:
32
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:
0.000377
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000147
AC:
37
AN:
251088
Hom.:
0
AF XY:
0.000140
AC XY:
19
AN XY:
135774
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:
0.0000327
Gnomad FIN exome
AF:
0.000277
Gnomad NFE exome
AF:
0.000247
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000105
AC:
153
AN:
1461776
Hom.:
1
Cov.:
34
AF XY:
0.000110
AC XY:
80
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000206
Gnomad4 NFE exome
AF:
0.000121
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152108
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74290
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:
0.000377
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000184
Hom.:
0
Bravo
AF:
0.0000982
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000327
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 GeneticsDec 08, 2023The c.857C>G (p.S286C) alteration is located in exon 7 (coding exon 7) of the PLBD1 gene. This alteration results from a C to G substitution at nucleotide position 857, causing the serine (S) at amino acid position 286 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
Pathogenic
0.96
BayesDel_addAF
Uncertain
0.094
D
BayesDel_noAF
Pathogenic
0.22
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.21
T
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.95
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.97
D
M_CAP
Benign
0.063
D
MetaRNN
Pathogenic
0.85
D
MetaSVM
Uncertain
-0.013
T
MutationAssessor
Pathogenic
4.2
H
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.72
T
PROVEAN
Pathogenic
-4.7
D
REVEL
Pathogenic
0.75
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.92
MVP
0.50
MPC
0.77
ClinPred
0.94
D
GERP RS
5.5
Varity_R
0.80
gMVP
0.94

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: rs761954357; hg19: chr12-14664633; COSMIC: COSV53693448; API