chr12-14511391-T-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.1055A>Gā€‹(p.Asn352Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,460,978 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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000068 ( 0 hom. )

Consequence

PLBD1
NM_024829.6 missense

Scores

8
4
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49
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, 0.871

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLBD1NM_024829.6 linkuse as main transcriptc.1055A>G p.Asn352Ser missense_variant 8/11 ENST00000240617.10 NP_079105.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLBD1ENST00000240617.10 linkuse as main transcriptc.1055A>G p.Asn352Ser missense_variant 8/111 NM_024829.6 ENSP00000240617 P1
PLBD1ENST00000541800.6 linkuse as main transcriptn.678A>G non_coding_transcript_exon_variant 3/33

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000479
AC:
12
AN:
250574
Hom.:
0
AF XY:
0.0000664
AC XY:
9
AN XY:
135470
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000653
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1460978
Hom.:
0
Cov.:
34
AF XY:
0.0000110
AC XY:
8
AN XY:
726830
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000227
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.0000412
AC:
5

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 GeneticsSep 20, 2023The c.1055A>G (p.N352S) alteration is located in exon 8 (coding exon 8) of the PLBD1 gene. This alteration results from a A to G substitution at nucleotide position 1055, causing the asparagine (N) at amino acid position 352 to be replaced by a serine (S). 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
0.18
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.093
T
Eigen
Pathogenic
0.99
Eigen_PC
Pathogenic
0.91
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.067
D
MetaRNN
Pathogenic
0.87
D
MetaSVM
Uncertain
-0.13
T
MutationAssessor
Pathogenic
3.8
H
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.46
T
PROVEAN
Pathogenic
-4.8
D
REVEL
Uncertain
0.59
Sift
Uncertain
0.0050
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.82
MutPred
0.83
Gain of catalytic residue at N352 (P = 0.0072);
MVP
0.33
MPC
0.69
ClinPred
0.86
D
GERP RS
5.8
Varity_R
0.52
gMVP
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs781663830; hg19: chr12-14664325; API