chr17-7237452-A-G
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_024297.3(PHF23):āc.92T>Cā(p.Ile31Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,952 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 0.000099 ( 0 hom., cov: 32)
Exomes š: 0.000013 ( 0 hom. )
Consequence
PHF23
NM_024297.3 missense
NM_024297.3 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 8.88
Genes affected
PHF23 (HGNC:28428): (PHD finger protein 23) Predicted to enable metal ion binding activity. Involved in negative regulation of autophagosome assembly; negative regulation of autophagosome maturation; and positive regulation of protein ubiquitination. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.10194394).
BS2
High AC in GnomAd4 at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHF23 | NM_024297.3 | c.92T>C | p.Ile31Thr | missense_variant | 3/5 | ENST00000320316.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHF23 | ENST00000320316.8 | c.92T>C | p.Ile31Thr | missense_variant | 3/5 | 1 | NM_024297.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000987 AC: 15AN: 152012Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249542Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135386
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461822Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727224
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GnomAD4 genome AF: 0.0000986 AC: 15AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74372
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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 | Mar 02, 2023 | The c.92T>C (p.I31T) alteration is located in exon 3 (coding exon 3) of the PHF23 gene. This alteration results from a T to C substitution at nucleotide position 92, causing the isoleucine (I) at amino acid position 31 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Uncertain
N;.;N;.;.;.
REVEL
Uncertain
Sift
Uncertain
D;.;D;.;.;.
Sift4G
Uncertain
D;D;D;D;.;D
Polyphen
B;.;.;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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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