chr12-14542283-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024829.6(PLBD1):ā€‹c.344A>Gā€‹(p.Asn115Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000518 in 1,603,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.000057 ( 0 hom. )

Consequence

PLBD1
NM_024829.6 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.942
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06088367).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLBD1NM_024829.6 linkuse as main transcriptc.344A>G p.Asn115Ser missense_variant 3/11 ENST00000240617.10 NP_079105.4
LOC101928317XR_001749015.2 linkuse as main transcriptn.747+1034T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLBD1ENST00000240617.10 linkuse as main transcriptc.344A>G p.Asn115Ser missense_variant 3/111 NM_024829.6 ENSP00000240617 P1
ENST00000655882.1 linkuse as main transcriptn.762+1034T>C intron_variant, non_coding_transcript_variant
PLBD1ENST00000540572.1 linkuse as main transcriptc.203A>G p.Asn68Ser missense_variant 3/55 ENSP00000438367
PLBD1ENST00000541618.1 linkuse as main transcriptc.*1A>G 3_prime_UTR_variant, NMD_transcript_variant 2/65 ENSP00000441278

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152234
Hom.:
0
Cov.:
33
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251222
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135790
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000565
AC:
82
AN:
1450838
Hom.:
0
Cov.:
28
AF XY:
0.0000554
AC XY:
40
AN XY:
722460
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000690
Gnomad4 OTH exome
AF:
0.000100
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152234
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74384
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:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000546
EpiControl
AF:
0.000119

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 30, 2021The c.344A>G (p.N115S) alteration is located in exon 3 (coding exon 3) of the PLBD1 gene. This alteration results from a A to G substitution at nucleotide position 344, causing the asparagine (N) at amino acid position 115 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
0.066
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
13
DANN
Benign
0.94
DEOGEN2
Benign
0.00056
T;.
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.54
FATHMM_MKL
Benign
0.35
N
LIST_S2
Benign
0.67
T;T
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.061
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.65
N;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.28
N;N
REVEL
Benign
0.044
Sift
Benign
0.38
T;T
Sift4G
Benign
0.39
T;.
Polyphen
0.0
B;.
Vest4
0.12
MutPred
0.50
Gain of catalytic residue at H117 (P = 8e-04);.;
MVP
0.030
MPC
0.16
ClinPred
0.022
T
GERP RS
0.84
Varity_R
0.019
gMVP
0.33

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: rs766149414; hg19: chr12-14695217; API