Genetic Variant PHF20L1:p.Lys549Glu (chr8-132825272-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_016018.5(PHF20L1):c.1645A>G(p.Lys549Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,423,488 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: 0.0000014 ( 0 hom. )

Consequence

PHF20L1
NM_016018.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.74

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:

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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=0.14888406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF20L1	NM_016018.5 link	c.1645A>G	p.Lys549Glu	missense_variant	Exon 14 of 21	ENST00000395386.7	NP_057102.4	A8MW92-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF20L1	ENST00000395386.7 link	c.1645A>G	p.Lys549Glu	missense_variant	Exon 14 of 21	5	NM_016018.5	ENSP00000378784.2		A8MW92-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000412

AC:

AN:

242612

Hom.:

AF XY:

0.00000757

AC XY:

AN XY:

132036

show subpopulations

Gnomad AFR exome

AF:

0.0000659

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000141

AC:

AN:

1423488

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

710238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000626

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:

0.00

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

Oct 22, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1645A>G (p.K549E) alteration is located in exon 14 (coding exon 13) of the PHF20L1 gene. This alteration results from a A to G substitution at nucleotide position 1645, causing the lysine (K) at amino acid position 549 to be replaced by a glutamic acid (E). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.086

T;T;T;T

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

D;D;.;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.;L;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.6

.;.;N;N

REVEL

Benign

0.069

Sift

Uncertain

0.0050

.;.;D;D

Sift4G

Uncertain

0.014

D;D;D;D

Polyphen

0.26

B;.;B;B

Vest4

0.30

MutPred

0.16

Loss of methylation at K549 (P = 0.0085);.;Loss of methylation at K549 (P = 0.0085);.;

MVP

0.14

MPC

0.49

ClinPred

0.32

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.16

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