chrX-53940296-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_015107.3(PHF8):c.2870G>A(p.Arg957His) variant causes a missense change. The variant allele was found at a frequency of 0.0000064 in 1,092,946 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.0000064 ( 0 hom. 2 hem. )
Failed GnomAD Quality Control
Consequence
PHF8
NM_015107.3 missense
NM_015107.3 missense
Scores
1
3
11
Clinical Significance
Conservation
PhyloP100: 5.08
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 Likely_benign. Variant got -1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, PHF8
BP4
?
Computational evidence support a benign effect (MetaRNN=0.16497797).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHF8 | NM_015107.3 | c.2870G>A | p.Arg957His | missense_variant | 21/22 | ENST00000338154.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHF8 | ENST00000338154.11 | c.2870G>A | p.Arg957His | missense_variant | 21/22 | 1 | NM_015107.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 111554Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33752 FAILED QC
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GnomAD3 exomes AF: 0.00000587 AC: 1AN: 170389Hom.: 0 AF XY: 0.0000177 AC XY: 1AN XY: 56619
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GnomAD4 exome AF: 0.00000640 AC: 7AN: 1092946Hom.: 0 Cov.: 31 AF XY: 0.00000557 AC XY: 2AN XY: 358856
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GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 111554Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33752
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2020 | The c.2870G>A (p.R957H) alteration is located in exon 21 (coding exon 20) of the PHF8 gene. This alteration results from a G to A substitution at nucleotide position 2870, causing the arginine (R) at amino acid position 957 to be replaced by a histidine (H). The p.R957H alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
1.0
.;D;.
Vest4
MutPred
0.20
.;Loss of MoRF binding (P = 0.1037);.;
MVP
MPC
2.6
ClinPred
D
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