9-120858025-C-G
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_015651.3(PHF19):āc.1662G>Cā(p.Lys554Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 32)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
PHF19
NM_015651.3 missense
NM_015651.3 missense
Scores
10
9
Clinical Significance
Conservation
PhyloP100: 1.81
Genes affected
PHF19 (HGNC:24566): (PHD finger protein 19) Enables methylated histone binding activity. Involved in positive regulation of histone H3-K27 methylation. Colocalizes with ESC/E(Z) complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.25596455).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PHF19 | NM_015651.3 | c.1662G>C | p.Lys554Asn | missense_variant | 15/15 | ENST00000373896.8 | NP_056466.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PHF19 | ENST00000373896.8 | c.1662G>C | p.Lys554Asn | missense_variant | 15/15 | 2 | NM_015651.3 | ENSP00000363003.3 | ||
PHF19 | ENST00000616568.5 | c.1719G>C | p.Lys573Asn | missense_variant | 15/15 | 1 | ENSP00000483946.1 | |||
PHF19 | ENST00000487555.5 | n.997G>C | non_coding_transcript_exon_variant | 9/9 | 1 | |||||
PHF19 | ENST00000419155.5 | c.1035G>C | p.Lys345Asn | missense_variant | 10/10 | 2 | ENSP00000407433.1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152254Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461820Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727224
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74382
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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 | Nov 14, 2023 | The c.1662G>C (p.K554N) alteration is located in exon 15 (coding exon 14) of the PHF19 gene. This alteration results from a G to C substitution at nucleotide position 1662, causing the lysine (K) at amino acid position 554 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;.;M
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D
REVEL
Benign
Sift
Uncertain
D;.;D
Sift4G
Benign
T;T;T
Polyphen
0.90
.;.;P
Vest4
MutPred
0.36
.;.;Loss of methylation at K554 (P = 0.0236);
MVP
MPC
2.2
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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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