chrX-53940235-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2
The NM_015107.3(PHF8):c.2931C>T(p.Val977=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000755 in 1,192,477 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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 0.000027 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.0000056 ( 0 hom. 3 hem. )
Consequence
PHF8
NM_015107.3 synonymous
NM_015107.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.685
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant X-53940235-G-A is Benign according to our data. Variant chrX-53940235-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1797821.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.685 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000268 (3/112097) while in subpopulation AMR AF= 0.000284 (3/10553). AF 95% confidence interval is 0.000077. There are 0 homozygotes in gnomad4. There are 1 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAdExome at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHF8 | NM_015107.3 | c.2931C>T | p.Val977= | synonymous_variant | 21/22 | ENST00000338154.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHF8 | ENST00000338154.11 | c.2931C>T | p.Val977= | synonymous_variant | 21/22 | 1 | NM_015107.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000268 AC: 3AN: 112097Hom.: 0 Cov.: 22 AF XY: 0.0000292 AC XY: 1AN XY: 34239
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GnomAD3 exomes AF: 0.0000339 AC: 5AN: 147334Hom.: 0 AF XY: 0.0000447 AC XY: 2AN XY: 44786
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GnomAD4 exome AF: 0.00000555 AC: 6AN: 1080380Hom.: 0 Cov.: 31 AF XY: 0.00000853 AC XY: 3AN XY: 351844
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 26, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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