Genetic Variant PHF20L1:p.Lys561Arg (chr8-132825309-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016018.5(PHF20L1):c.1682A>G(p.Lys561Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000424 in 1,533,606 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 1 hom. )

Consequence

PHF20L1
NM_016018.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24

Publications

0 publications found

Variant links:

Genes affected

PHF20L1 (HGNC:24280): (PHD finger protein 20 like 1) Predicted to enable metal ion binding activity. Predicted to be involved in histone acetylation and regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of NSL complex. [provided by Alliance of Genome Resources, Apr 2022]

PHF20L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023260474).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016018.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PHF20L1	NM_016018.5	MANE Select	c.1682A>G	p.Lys561Arg	missense	Exon 14 of 21	NP_057102.4
PHF20L1	NM_001438309.1		c.1697A>G	p.Lys566Arg	missense	Exon 14 of 21	NP_001425238.1
PHF20L1	NM_001438310.1		c.1694A>G	p.Lys565Arg	missense	Exon 14 of 21	NP_001425239.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHF20L1	ENST00000395386.7	TSL:5 MANE Select	c.1682A>G	p.Lys561Arg	missense	Exon 14 of 21	ENSP00000378784.2	A8MW92-1
PHF20L1	ENST00000315808.14	TSL:1	n.2194A>G		non_coding_transcript_exon	Exon 14 of 14
PHF20L1	ENST00000939789.1		c.1697A>G	p.Lys566Arg	missense	Exon 14 of 21	ENSP00000609848.1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.0000260

AC:

AN:

230904

AF XY:

0.0000317

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000918

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000979

Gnomad OTH exome

AF:

0.000358

GnomAD4 exome

AF:

0.0000232

AC:

AN:

1381444

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

691570

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30968

American (AMR)

AF:

0.000374

AC:

AN:

42830

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25188

East Asian (EAS)

AF:

0.00

AC:

AN:

38802

South Asian (SAS)

AF:

0.00

AC:

AN:

83666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52802

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5578

European-Non Finnish (NFE)

AF:

0.00000766

AC:

AN:

1044184

Other (OTH)

AF:

0.000139

AC:

AN:

57426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.422

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000217

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41550

American (AMR)

AF:

0.00190

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67954

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000338

Hom.:

Bravo

AF:

0.000438

ExAC

AF:

0.0000166

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.035

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.78

M_CAP

Benign

0.0060

MetaRNN

Benign

0.023

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

3.2

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.66

REVEL

Benign

0.024

Sift

Pathogenic

0.0

Sift4G

Benign

0.23

Polyphen

0.0090

Vest4

0.19

MVP

0.068

MPC

0.23

ClinPred

0.11

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.18

Mutation Taster

=290/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over