Variant 20-35871757-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016436.5(PHF20):c.1210A>G(p.Met404Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000654 in 1,613,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00067 ( 0 hom. )

Consequence

PHF20
NM_016436.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

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=0.02576676).

BS2

High AC in GnomAd at 80 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF20	NM_016436.5 linkuse as main transcript	c.1210A>G	p.Met404Val	missense_variant	9/18	ENST00000374012.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF20	ENST00000374012.8 linkuse as main transcript	c.1210A>G	p.Met404Val	missense_variant	9/18	1	NM_016436.5	P1	Q9BVI0-1

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000461

AC:

116

AN:

251392

Hom.:

AF XY:

0.000464

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.000897

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000668

AC:

977

AN:

1461616

Hom.:

Cov.:

AF XY:

0.000641

AC XY:

466

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.000580

Gnomad4 NFE exome

AF:

0.000818

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000519

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.00115

Hom.:

Bravo

AF:

0.000465

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000511

AC:

EpiCase

AF:

0.000764

EpiControl

AF:

0.000889

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

Jul 09, 2021

The c.1210A>G (p.M404V) alteration is located in exon 9 (coding exon 8) of the PHF20 gene. This alteration results from a A to G substitution at nucleotide position 1210, causing the methionine (M) at amino acid position 404 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

0.066

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

Cadd

Benign

Dann

Benign

0.64

DEOGEN2

Benign

0.010

T;T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.60

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.;.

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.60

N;N;N

REVEL

Benign

0.037

Sift

Benign

0.34

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.21

B;.;.

Vest4

0.31

MVP

0.21

MPC

0.50

ClinPred

0.023

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.035

gMVP

0.23

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

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