Variant 17-7237636-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_024297.3(PHF23):c.59A>G(p.Glu20Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,613,856 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 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

PHF23
NM_024297.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.55

Variant links:

Genes affected

PHF23 (HGNC:28428): (PHD finger protein 23) Predicted to enable metal ion binding activity. Involved in negative regulation of autophagosome assembly; negative regulation of autophagosome maturation; and positive regulation of protein ubiquitination. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PHF23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.082411885).

BS2

High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF23	NM_024297.3 linkuse as main transcript	c.59A>G	p.Glu20Gly	missense_variant	2/5	ENST00000320316.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF23	ENST00000320316.8 linkuse as main transcript	c.59A>G	p.Glu20Gly	missense_variant	2/5	1	NM_024297.3	P1	Q9BUL5-1

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000761

AC:

AN:

249516

Hom.:

AF XY:

0.0000739

AC XY:

AN XY:

135384

show subpopulations

Gnomad AFR exome

AF:

0.00116

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:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1461738

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000230

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.000821

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000425

Hom.:

Bravo

AF:

0.000223

ESP6500AA

AF:

0.000764

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000910

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Aug 17, 2021

The c.59A>G (p.E20G) alteration is located in exon 2 (coding exon 2) of the PHF23 gene. This alteration results from a A to G substitution at nucleotide position 59, causing the glutamic acid (E) at amino acid position 20 to be replaced by a glycine (G). 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

Pathogenic

0.57

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

T;.;.;T;T;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.81

T;T;T;T;T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.082

T;T;T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.48

N;N;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-2.3

N;.;N;.;.;.

REVEL

Benign

0.11

Sift

Uncertain

0.0050

D;.;D;.;.;.

Sift4G

Uncertain

0.057

T;T;T;D;.;D

Polyphen

1.0

D;.;.;.;.;.

Vest4

0.52

MVP

0.043

MPC

1.0

ClinPred

0.15

GERP RS

4.8

Varity_R

0.16

gMVP

0.42

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