rs201824053
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_015107.3(PHF8):c.2199C>T(p.Ser733=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,204,853 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 69 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000080 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.00016 ( 0 hom. 69 hem. )
Consequence
PHF8
NM_015107.3 synonymous
NM_015107.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0970
Genes affected
PHF8 (HGNC:20672): (PHD finger protein 8) The protein encoded by this gene is a histone lysine demethylase that preferentially acts on histones in the monomethyl or dimethyl states. The encoded protein requires Fe(2+) ion, 2-oxoglutarate, and oxygen for its catalytic activity. The protein has an N-terminal PHD finger and a central Jumonji C domain. This gene is thought to function as a transcription activator. Defects in this gene are a cause of syndromic X-linked Siderius type intellectual disability (MRXSSD) and over-expression of this gene is associated with several forms of cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant X-53985158-G-A is Benign according to our data. Variant chrX-53985158-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 436308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.097 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0000803 (9/112120) while in subpopulation NFE AF= 0.000169 (9/53235). AF 95% confidence interval is 0.0000872. There are 0 homozygotes in gnomad4. There are 0 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAdExome at 4 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHF8 | NM_015107.3 | c.2199C>T | p.Ser733= | synonymous_variant | 18/22 | ENST00000338154.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHF8 | ENST00000338154.11 | c.2199C>T | p.Ser733= | synonymous_variant | 18/22 | 1 | NM_015107.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000803 AC: 9AN: 112120Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34282
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GnomAD3 exomes AF: 0.0000588 AC: 10AN: 170011Hom.: 0 AF XY: 0.0000708 AC XY: 4AN XY: 56523
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GnomAD4 exome AF: 0.000165 AC: 180AN: 1092733Hom.: 0 Cov.: 31 AF XY: 0.000192 AC XY: 69AN XY: 358605
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GnomAD4 genome ? AF: 0.0000803 AC: 9AN: 112120Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34282
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 01, 2016 | - - |
PHF8-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 19, 2019 | 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
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at