chr2-218633716-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_032726.4(PLCD4):āc.1561T>Cā(p.Ser521Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000514 in 1,613,802 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 (ā ).
Frequency
Genomes: š 0.000053 ( 0 hom., cov: 32)
Exomes š: 0.000051 ( 0 hom. )
Consequence
PLCD4
NM_032726.4 missense
NM_032726.4 missense
Scores
3
13
3
Clinical Significance
Conservation
PhyloP100: 4.17
Genes affected
PLCD4 (HGNC:9062): (phospholipase C delta 4) This gene encodes a member of the delta class of phospholipase C enzymes. Phospholipase C enzymes play a critical role in many cellular processes by hydrolyzing phosphatidylinositol 4,5-bisphosphate into two intracellular second messengers, inositol 1,4,5-trisphosphate and diacylglycerol. Expression of this gene may be a marker for cancer. [provided by RefSeq, Jan 2011]
ZNF142 (HGNC:12927): (zinc finger protein 142) The protein encoded by this gene belongs to the Kruppel family of C2H2-type zinc finger proteins. It contains 31 C2H2-type zinc fingers and may be involved in transcriptional regulation. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]
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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, 0.881
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCD4 | NM_032726.4 | c.1561T>C | p.Ser521Pro | missense_variant | 11/16 | ENST00000450993.7 | |
ZNF142 | NM_001379659.1 | c.*4623A>G | 3_prime_UTR_variant | 11/11 | ENST00000411696.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCD4 | ENST00000450993.7 | c.1561T>C | p.Ser521Pro | missense_variant | 11/16 | 1 | NM_032726.4 | P1 | |
ZNF142 | ENST00000411696.7 | c.*4623A>G | 3_prime_UTR_variant | 11/11 | 5 | NM_001379659.1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152108Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000763 AC: 19AN: 249132Hom.: 0 AF XY: 0.000104 AC XY: 14AN XY: 135186
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GnomAD4 exome AF: 0.0000513 AC: 75AN: 1461694Hom.: 0 Cov.: 31 AF XY: 0.0000578 AC XY: 42AN XY: 727128
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74308
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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 submitter | clinical testing | Ambry Genetics | Apr 19, 2024 | The c.1561T>C (p.S521P) alteration is located in exon 11 (coding exon 10) of the PLCD4 gene. This alteration results from a T to C substitution at nucleotide position 1561, causing the serine (S) at amino acid position 521 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;D;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;.
Vest4
MutPred
Loss of phosphorylation at S521 (P = 0.0869);Loss of phosphorylation at S521 (P = 0.0869);.;
MVP
MPC
ClinPred
D
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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