20-35913291-A-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_016436.5(PHF20):c.1604A>T(p.Glu535Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000349 in 1,603,360 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: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

PHF20
NM_016436.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.68

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:

Genome browser will be placed here

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=0.024751186).

BS2

High AC in GnomAd at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF20	NM_016436.5 linkuse as main transcript	c.1604A>T	p.Glu535Val	missense_variant	11/18	ENST00000374012.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF20	ENST00000374012.8 linkuse as main transcript	c.1604A>T	p.Glu535Val	missense_variant	11/18	1	NM_016436.5	P1	Q9BVI0-1
PHF20	ENST00000374000.8 linkuse as main transcript	c.1604A>T	p.Glu535Val	missense_variant	12/12	1
PHF20	ENST00000481202.5 linkuse as main transcript	n.1610A>T		non_coding_transcript_exon_variant	10/10	1
PHF20	ENST00000339089.10 linkuse as main transcript	c.1604A>T	p.Glu535Val	missense_variant	12/12	2

Frequencies

GnomAD3 genomes

AF:

0.0000525

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000143

AC:

AN:

231548

Hom.:

AF XY:

0.000135

AC XY:

AN XY:

125546

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000311

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00187

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000331

AC:

AN:

1451118

Hom.:

Cov.:

AF XY:

0.0000333

AC XY:

AN XY:

721418

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000234

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000707

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000317

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Apr 18, 2023

The c.1604A>T (p.E535V) alteration is located in exon 11 (coding exon 10) of the PHF20 gene. This alteration results from a A to T substitution at nucleotide position 1604, causing the glutamic acid (E) at amino acid position 535 to be replaced by a valine (V). 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

0.32

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.28

T;T;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.025

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.34

N;.;.

MutationTaster

Benign

0.56

D;D

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.1

D;N;D

REVEL

Benign

0.072

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

0.70

P;.;.

Vest4

0.26

MutPred

0.32

Loss of solvent accessibility (P = 0.0431);Loss of solvent accessibility (P = 0.0431);Loss of solvent accessibility (P = 0.0431);

MVP

0.29

MPC

0.48

ClinPred

0.19

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over