chr3-155481410-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_014996.4(PLCH1):c.4616G>A(p.Arg1539Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000015 in 1,461,882 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
PLCH1
NM_014996.4 missense
NM_014996.4 missense
Scores
5
1
8
Clinical Significance
Conservation
PhyloP100: 4.65
Genes affected
PLCH1 (HGNC:29185): (phospholipase C eta 1) PLCH1 is a member of the PLC-eta family of the phosphoinositide-specific phospholipase C (PLC) superfamily of enzymes that cleave phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) to generate second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) (Hwang et al., 2005 [PubMed 15702972]).[supplied by OMIM, Jun 2009]
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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=0.388812).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCH1 | NM_014996.4 | c.4616G>A | p.Arg1539Gln | missense_variant | 23/23 | ENST00000460012.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCH1 | ENST00000460012.7 | c.4616G>A | p.Arg1539Gln | missense_variant | 23/23 | 5 | NM_014996.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251460Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135910
GnomAD3 exomes
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GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461882Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727244
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
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33
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5
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 | Dec 28, 2022 | The c.4640G>A (p.R1547Q) alteration is located in exon 23 (coding exon 23) of the PLCH1 gene. This alteration results from a G to A substitution at nucleotide position 4640, causing the arginine (R) at amino acid position 1547 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Benign
T
REVEL
Benign
Polyphen
1.0
.;D;D
Vest4
0.39, 0.47
MutPred
0.28
.;Gain of glycosylation at T1543 (P = 0.0343);.;
MVP
MPC
0.33
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
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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