chrX-53940370-G-C
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_015107.3(PHF8):āc.2796C>Gā(p.Ser932=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,095,855 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: not found (cov: 22)
Exomes š: 0.0000027 ( 0 hom. 2 hem. )
Consequence
PHF8
NM_015107.3 synonymous
NM_015107.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.903
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 -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant X-53940370-G-C is Benign according to our data. Variant chrX-53940370-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2660639.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.903 with no splicing effect.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00000274 (3/1095855) while in subpopulation MID AF= 0.000485 (2/4120). AF 95% confidence interval is 0.0000855. There are 0 homozygotes in gnomad4_exome. There are 2 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Hemizygotes in GnomAdExome4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHF8 | NM_015107.3 | c.2796C>G | p.Ser932= | synonymous_variant | 21/22 | ENST00000338154.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHF8 | ENST00000338154.11 | c.2796C>G | p.Ser932= | synonymous_variant | 21/22 | 1 | NM_015107.3 | P2 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000112 AC: 2AN: 179252Hom.: 0 AF XY: 0.0000156 AC XY: 1AN XY: 63986
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GnomAD4 exome AF: 0.00000274 AC: 3AN: 1095855Hom.: 0 Cov.: 31 AF XY: 0.00000552 AC XY: 2AN XY: 362017
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GnomAD4 genome Cov.: 22
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | PHF8: BP4, BP7 - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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