chrX-53940219-G-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_015107.3(PHF8):c.2947C>A(p.Arg983Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000059 in 1,187,288 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 0.000018 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.0000046 ( 0 hom. 2 hem. )
Consequence
PHF8
NM_015107.3 missense
NM_015107.3 missense
Scores
1
6
8
Clinical Significance
Conservation
PhyloP100: 3.48
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=0.2456179).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHF8 | NM_015107.3 | c.2947C>A | p.Arg983Ser | missense_variant | 21/22 | ENST00000338154.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHF8 | ENST00000338154.11 | c.2947C>A | p.Arg983Ser | missense_variant | 21/22 | 1 | NM_015107.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000179 AC: 2AN: 112016Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34162
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GnomAD4 exome AF: 0.00000465 AC: 5AN: 1075272Hom.: 0 Cov.: 31 AF XY: 0.00000572 AC XY: 2AN XY: 349910
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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 | Aug 04, 2018 | The p.R983S variant (also known as c.2947C>A), located in coding exon 20 of the PHF8 gene, results from a C to A substitution at nucleotide position 2947. The arginine at codon 983 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
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
Uncertain
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
0.98
.;D;.
Vest4
MutPred
0.24
.;Gain of phosphorylation at R1019 (P = 0.0378);.;
MVP
MPC
2.0
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