Variant chr8-132798801-G-A 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_016018.5(PHF20L1):c.370G>A(p.Val124Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,457,338 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: 0.0000021 ( 0 hom. )

Consequence

PHF20L1
NM_016018.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.78

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:

PHF20L1 (HGNC:):

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=0.25216967).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF20L1	NM_016018.5 linkuse as main transcript	c.370G>A	p.Val124Ile	missense_variant	5/21	ENST00000395386.7	NP_057102.4	A8MW92-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF20L1	ENST00000395386.7 linkuse as main transcript	c.370G>A	p.Val124Ile	missense_variant	5/21	5	NM_016018.5	ENSP00000378784.2		A8MW92-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000809

AC:

AN:

247216

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133628

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1457338

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724952

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000450

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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 23, 2023

The c.370G>A (p.V124I) alteration is located in exon 5 (coding exon 4) of the PHF20L1 gene. This alteration results from a G to A substitution at nucleotide position 370, causing the valine (V) at amino acid position 124 to be replaced by an isoleucine (I). 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

0.28

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;.;T;.;.;T;.;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

D;D;D;.;D;D;D;D;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.25

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.61

N;.;.;N;.;N;.;.;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.59

.;.;N;N;.;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.080

.;.;T;D;.;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T;T;T;T;T

Polyphen

0.20

B;.;B;B;.;D;.;.;D

Vest4

0.26

MutPred

0.33

Loss of MoRF binding (P = 0.1214);Loss of MoRF binding (P = 0.1214);Loss of MoRF binding (P = 0.1214);Loss of MoRF binding (P = 0.1214);Loss of MoRF binding (P = 0.1214);Loss of MoRF binding (P = 0.1214);Loss of MoRF binding (P = 0.1214);.;Loss of MoRF binding (P = 0.1214);

MVP

0.11

MPC

2.2

ClinPred

0.42

GERP RS

6.0

Varity_R

0.12

gMVP

0.39

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