rs141256799
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_004426.3(PHC1):c.2726G>A(p.Gly909Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000103 in 1,605,378 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 0.00062 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000050 ( 0 hom. )
Consequence
PHC1
NM_004426.3 missense
NM_004426.3 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 5.50
Genes affected
PHC1 (HGNC:3182): (polyhomeotic homolog 1) This gene is a homolog of the Drosophila polyhomeotic gene, which is a member of the Polycomb group of genes. The gene product is a component of a multimeric protein complex that contains EDR2 and the vertebrate Polycomb protein BMH1. The gene product, the EDR2 protein, and the Drosophila polyhomeotic protein share 2 highly conserved domains, named homology domains I and II. These domains are involved in protein-protein interactions and may mediate heterodimerization of the protein encoded by this gene and the EDR2 protein. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.00974828).
BP6
?
Variant 12-8937926-G-A is Benign according to our data. Variant chr12-8937926-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 436305.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHC1 | NM_004426.3 | c.2726G>A | p.Gly909Glu | missense_variant | 14/15 | ENST00000544916.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHC1 | ENST00000544916.6 | c.2726G>A | p.Gly909Glu | missense_variant | 14/15 | 1 | NM_004426.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000618 AC: 94AN: 152174Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000164 AC: 41AN: 250422Hom.: 0 AF XY: 0.000148 AC XY: 20AN XY: 135356
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GnomAD4 exome AF: 0.0000495 AC: 72AN: 1453086Hom.: 0 Cov.: 28 AF XY: 0.0000484 AC XY: 35AN XY: 723362
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GnomAD4 genome ? AF: 0.000617 AC: 94AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.000725 AC XY: 54AN XY: 74462
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 01, 2016 | - - |
PHC1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 18, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
D;.;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
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