chr12-14536571-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024829.6(PLBD1):ā€‹c.698A>Gā€‹(p.Lys233Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,750 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

PLBD1
NM_024829.6 missense, splice_region

Scores

4
8
7
Splicing: ADA: 0.9944
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.27
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLBD1NM_024829.6 linkuse as main transcriptc.698A>G p.Lys233Arg missense_variant, splice_region_variant 5/11 ENST00000240617.10 NP_079105.4
LOC101928317XR_001749015.2 linkuse as main transcriptn.588+671T>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.698A>G p.Lys233Arg missense_variant, splice_region_variant 5/111 NM_024829.6 ENSP00000240617 P1
ENST00000655882.1 linkuse as main transcriptn.603+671T>C intron_variant, non_coding_transcript_variant
PLBD1ENST00000541618.1 linkuse as main transcriptc.*355A>G splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant 4/65 ENSP00000441278

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251318
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135836
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000993
Gnomad EAS exome
AF:
0.00
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:
0.00000410
AC:
6
AN:
1461750
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
AN XY:
727166
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000555
Hom.:
0
Bravo
AF:
0.00000756

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 GeneticsNov 10, 2022The c.698A>G (p.K233R) alteration is located in exon 5 (coding exon 5) of the PLBD1 gene. This alteration results from a A to G substitution at nucleotide position 698, causing the lysine (K) at amino acid position 233 to be replaced by an arginine (R). 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
0.19
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Benign
0.026
T
Eigen
Pathogenic
0.68
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.68
D
MetaSVM
Benign
-0.84
T
MutationAssessor
Uncertain
2.5
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-2.2
N
REVEL
Uncertain
0.32
Sift
Benign
0.14
T
Sift4G
Uncertain
0.019
D
Polyphen
0.96
D
Vest4
0.82
MVP
0.22
MPC
0.70
ClinPred
0.92
D
GERP RS
5.9
Varity_R
0.25
gMVP
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
0.99
dbscSNV1_RF
Pathogenic
0.91
SpliceAI score (max)
0.43
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.43
Position offset: -1

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: rs1353935296; hg19: chr12-14689505; API