rs375683615
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_006225.4(PLCD1):c.1657G>A(p.Ala553Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000123 in 1,613,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
PLCD1
NM_006225.4 missense
NM_006225.4 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 4.98
Genes affected
PLCD1 (HGNC:9060): (phospholipase C delta 1) This gene encodes a member of the phospholipase C family. Phospholipase C isozymes play critical roles in intracellular signal transduction by catalyzing the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into the second messengers diacylglycerol (DAG) and inositol triphosphate (IP3). The encoded protein functions as a tumor suppressor in several types of cancer, and mutations in this gene are a cause of hereditary leukonychia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.2745982).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLCD1 | NM_006225.4 | c.1657G>A | p.Ala553Thr | missense_variant | 11/15 | ENST00000334661.5 | NP_006216.2 | |
PLCD1 | NM_001130964.2 | c.1720G>A | p.Ala574Thr | missense_variant | 11/15 | NP_001124436.1 | ||
PLCD1 | NR_024071.2 | n.1884G>A | non_coding_transcript_exon_variant | 10/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLCD1 | ENST00000334661.5 | c.1657G>A | p.Ala553Thr | missense_variant | 11/15 | 1 | NM_006225.4 | ENSP00000335600.4 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152232Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000183 AC: 46AN: 251100Hom.: 0 AF XY: 0.000236 AC XY: 32AN XY: 135754
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GnomAD4 exome AF: 0.000118 AC: 173AN: 1461752Hom.: 0 Cov.: 33 AF XY: 0.000129 AC XY: 94AN XY: 727172
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GnomAD4 genome AF: 0.000164 AC: 25AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74366
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Nonsyndromic congenital nail disorder 3 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 10, 2011 | - - |
PLCD1-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 13, 2024 | The PLCD1 c.1720G>A variant is predicted to result in the amino acid substitution p.Ala574Thr. This variant has been reported in the heterozygous state to segregate with leukonychia in a family (Kiuru et al. 2011. PubMed ID: 21665001). Functional studies showed that this variant results in ~40% increased enzyme activity (rat ortholog p.Ala553Thr, Nomikos et al. 2016. PubMed ID: 27783455). This variant is reported in 0.10% of alleles in individuals of European (Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.91
.;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at