20-35863065-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016436.5(PHF20):​c.473C>T​(p.Ser158Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000207 in 1,450,620 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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PHF20
NM_016436.5 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.38
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2815888).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PHF20NM_016436.5 linkc.473C>T p.Ser158Leu missense_variant Exon 6 of 18 ENST00000374012.8 NP_057520.2 Q9BVI0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PHF20ENST00000374012.8 linkc.473C>T p.Ser158Leu missense_variant Exon 6 of 18 1 NM_016436.5 ENSP00000363124.3 Q9BVI0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000207
AC:
3
AN:
1450620
Hom.:
0
Cov.:
31
AF XY:
0.00000277
AC XY:
2
AN XY:
721832
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.473C>T (p.S158L) alteration is located in exon 6 (coding exon 5) of the PHF20 gene. This alteration results from a C to T substitution at nucleotide position 473, causing the serine (S) at amino acid position 158 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.056
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.035
T;T;T;.
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.87
D;D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.28
T;T;T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
1.8
L;.;.;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-1.7
N;N;N;N
REVEL
Benign
0.092
Sift
Uncertain
0.0060
D;D;D;D
Sift4G
Benign
0.14
T;T;T;T
Polyphen
0.61
P;.;.;.
Vest4
0.36
MutPred
0.19
Loss of phosphorylation at S158 (P = 0.0036);Loss of phosphorylation at S158 (P = 0.0036);Loss of phosphorylation at S158 (P = 0.0036);.;
MVP
0.28
MPC
0.74
ClinPred
0.86
D
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.14
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-34450987; API