rs149376854
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_004426.3(PHC1):āc.2238A>Gā(p.Gly746=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 1,613,332 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 Likely benign (ā ).
Frequency
Genomes: š 0.00030 ( 0 hom., cov: 32)
Exomes š: 0.00026 ( 0 hom. )
Consequence
PHC1
NM_004426.3 synonymous
NM_004426.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.24
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 -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 12-8934463-A-G is Benign according to our data. Variant chr12-8934463-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 436303.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.24 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHC1 | NM_004426.3 | c.2238A>G | p.Gly746= | synonymous_variant | 10/15 | ENST00000544916.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHC1 | ENST00000544916.6 | c.2238A>G | p.Gly746= | synonymous_variant | 10/15 | 1 | NM_004426.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000296 AC: 45AN: 152160Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000267 AC: 67AN: 250634Hom.: 0 AF XY: 0.000295 AC XY: 40AN XY: 135454
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GnomAD4 exome AF: 0.000261 AC: 381AN: 1461054Hom.: 0 Cov.: 32 AF XY: 0.000250 AC XY: 182AN XY: 726858
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GnomAD4 genome ? AF: 0.000296 AC: 45AN: 152278Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26AN XY: 74460
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 08, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at