chr12-14511577-G-A

Variant summary

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

The NM_024829.6(PLBD1):​c.979C>T​(p.Arg327Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,982 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

PLBD1
NM_024829.6 missense

Scores

8
6
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30
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, 0.853

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLBD1NM_024829.6 linkuse as main transcriptc.979C>T p.Arg327Cys 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.979C>T p.Arg327Cys missense_variant 7/111 NM_024829.6 ENSP00000240617 P1
PLBD1ENST00000541800.6 linkuse as main transcriptn.602C>T non_coding_transcript_exon_variant 2/33
PLBD1ENST00000541618.1 linkuse as main transcriptc.*636C>T 3_prime_UTR_variant, NMD_transcript_variant 6/65 ENSP00000441278

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152098
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251430
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461884
Hom.:
0
Cov.:
34
AF XY:
0.00000688
AC XY:
5
AN XY:
727246
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:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152098
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74276
show subpopulations
Gnomad4 AFR
AF:
0.0000724
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.00000824
AC:
1

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 GeneticsMay 25, 2022The c.979C>T (p.R327C) alteration is located in exon 7 (coding exon 7) of the PLBD1 gene. This alteration results from a C to T substitution at nucleotide position 979, causing the arginine (R) at amino acid position 327 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
0.69
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.062
T
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.083
D
MetaRNN
Pathogenic
0.85
D
MetaSVM
Benign
-0.73
T
MutationAssessor
Pathogenic
3.5
H
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.61
T
PROVEAN
Pathogenic
-5.7
D
REVEL
Uncertain
0.46
Sift
Uncertain
0.0070
D
Sift4G
Benign
0.064
T
Polyphen
1.0
D
Vest4
0.91
MutPred
0.62
Gain of catalytic residue at V328 (P = 0);
MVP
0.46
MPC
0.91
ClinPred
0.99
D
GERP RS
5.8
Varity_R
0.48
gMVP
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
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: rs764137177; hg19: chr12-14664511; COSMIC: COSV99554286; API