2-218634129-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032726.4(PLCD4):​c.1631C>T​(p.Thr544Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PLCD4
NM_032726.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.09
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27276343).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLCD4NM_032726.4 linkuse as main transcriptc.1631C>T p.Thr544Ile missense_variant 12/16 ENST00000450993.7 NP_116115.1 Q9BRC7-1
ZNF142NM_001379659.1 linkuse as main transcriptc.*4210G>A 3_prime_UTR_variant 11/11 ENST00000411696.7 NP_001366588.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLCD4ENST00000450993.7 linkuse as main transcriptc.1631C>T p.Thr544Ile missense_variant 12/161 NM_032726.4 ENSP00000388631.2 Q9BRC7-1
PLCD4ENST00000432688.5 linkuse as main transcriptc.1727C>T p.Thr576Ile missense_variant 13/175 ENSP00000396185.1 C9JEA7
PLCD4ENST00000417849.5 linkuse as main transcriptc.1631C>T p.Thr544Ile missense_variant 12/175 ENSP00000396942.1 Q9BRC7-1
ZNF142ENST00000411696 linkuse as main transcriptc.*4210G>A 3_prime_UTR_variant 11/115 NM_001379659.1 ENSP00000398798.3 A0A7P0N7C4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000407
AC:
1
AN:
245494
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
133080
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000334
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1459704
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
725890
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:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000827
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 GeneticsJun 26, 2024The c.1631C>T (p.T544I) alteration is located in exon 12 (coding exon 11) of the PLCD4 gene. This alteration results from a C to T substitution at nucleotide position 1631, causing the threonine (T) at amino acid position 544 to be replaced by an isoleucine (I). 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
0.15
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.46
CADD
Uncertain
24
DANN
Benign
0.94
DEOGEN2
Benign
0.31
T;T;T
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.10
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.69
T;.;T
M_CAP
Benign
0.045
D
MetaRNN
Benign
0.27
T;T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
0.84
L;L;.
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.9
N;N;N
REVEL
Benign
0.17
Sift
Benign
0.22
T;T;T
Sift4G
Benign
0.22
T;T;T
Polyphen
0.72
P;P;.
Vest4
0.23
MutPred
0.47
Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;
MVP
0.72
MPC
0.44
ClinPred
0.36
T
GERP RS
4.5
Varity_R
0.14
gMVP
0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs769313876; hg19: chr2-219498852; API