20-35914144-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_016436.5(PHF20):c.1772C>T(p.Pro591Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,614,016 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 1 hom. )
Consequence
PHF20
NM_016436.5 missense
NM_016436.5 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 1.78
Genes affected
PHF20 (HGNC:16098): (PHD finger protein 20) Predicted to enable DNA binding activity and metal ion binding activity. Involved in histone H4-K16 acetylation; histone H4-K5 acetylation; and histone H4-K8 acetylation. Located in cytosol; nuclear membrane; and nucleoplasm. Part of MLL1 complex and histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, PHF20
BP4
?
Computational evidence support a benign effect (MetaRNN=0.01682499).
BS2
?
High AC in GnomAd at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHF20 | NM_016436.5 | c.1772C>T | p.Pro591Leu | missense_variant | 12/18 | ENST00000374012.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHF20 | ENST00000374012.8 | c.1772C>T | p.Pro591Leu | missense_variant | 12/18 | 1 | NM_016436.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000724 AC: 11AN: 152020Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000259 AC: 65AN: 251266Hom.: 1 AF XY: 0.000272 AC XY: 37AN XY: 135818
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GnomAD4 exome AF: 0.000146 AC: 213AN: 1461878Hom.: 1 Cov.: 30 AF XY: 0.000169 AC XY: 123AN XY: 727236
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74368
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 18, 2021 | The c.1772C>T (p.P591L) alteration is located in exon 12 (coding exon 11) of the PHF20 gene. This alteration results from a C to T substitution at nucleotide position 1772, causing the proline (P) at amino acid position 591 to be replaced by a leucine (L). 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
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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