chr12-14536608-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024829.6(PLBD1):​c.661A>G​(p.Lys221Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PLBD1
NM_024829.6 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07990584).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLBD1NM_024829.6 linkuse as main transcriptc.661A>G p.Lys221Glu missense_variant 5/11 ENST00000240617.10 NP_079105.4
LOC101928317XR_001749015.2 linkuse as main transcriptn.588+708T>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.661A>G p.Lys221Glu missense_variant 5/111 NM_024829.6 ENSP00000240617 P1
ENST00000655882.1 linkuse as main transcriptn.603+708T>C intron_variant, non_coding_transcript_variant
PLBD1ENST00000541618.1 linkuse as main transcriptc.*318A>G 3_prime_UTR_variant, NMD_transcript_variant 4/65 ENSP00000441278

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

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 GeneticsFeb 15, 2023The c.661A>G (p.K221E) 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 661, causing the lysine (K) at amino acid position 221 to be replaced by a glutamic acid (E). 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
0.11
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
16
DANN
Benign
0.58
DEOGEN2
Benign
0.0014
T
Eigen
Benign
-0.93
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.062
N
LIST_S2
Benign
0.58
T
M_CAP
Benign
0.0071
T
MetaRNN
Benign
0.080
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.2
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-0.30
N
REVEL
Benign
0.058
Sift
Benign
0.56
T
Sift4G
Benign
0.65
T
Polyphen
0.0090
B
Vest4
0.26
MutPred
0.50
Loss of methylation at K221 (P = 4e-04);
MVP
0.055
MPC
0.29
ClinPred
0.098
T
GERP RS
3.5
Varity_R
0.095
gMVP
0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-14689542; API