Variant 20-35863337-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016436.5(PHF20):c.745C>T(p.Pro249Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PHF20
NM_016436.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.13

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]

PHF20 links:

PHF20 (HGNC:):

PHF20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11762902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF20	NM_016436.5 linkuse as main transcript	c.745C>T	p.Pro249Ser	missense_variant	6/18	ENST00000374012.8	NP_057520.2	Q9BVI0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF20	ENST00000374012.8 linkuse as main transcript	c.745C>T	p.Pro249Ser	missense_variant	6/18	1	NM_016436.5	ENSP00000363124.3		Q9BVI0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460006

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726360

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 11, 2024

The c.745C>T (p.P249S) 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 745, causing the proline (P) at amino acid position 249 to be replaced by a serine (S). 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

0.084

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

T;T;T;.

Eigen

Benign

-0.063

Eigen_PC

Benign

0.011

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.83

T;T;T;T

M_CAP

Benign

0.0098

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.76

N;N;N;N

REVEL

Benign

0.076

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Benign

0.70

T;T;T;T

Polyphen

0.0010

B;.;.;.

Vest4

0.043

MutPred

0.12

Gain of phosphorylation at P249 (P = 0.014);Gain of phosphorylation at P249 (P = 0.014);Gain of phosphorylation at P249 (P = 0.014);.;

MVP

0.39

MPC

0.52

ClinPred

0.39

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over