dbSNP rs374283851: PHF23:p.Arg228Pro (chr17-7236244-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

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

The NM_024297.3(PHF23):c.683G>C(p.Arg228Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R228Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PHF23
NM_024297.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.94

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16472977).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF23	NM_024297.3 link	c.683G>C	p.Arg228Pro	missense_variant	Exon 4 of 5	ENST00000320316.8	NP_077273.2	Q9BUL5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF23	ENST00000320316.8 link	c.683G>C	p.Arg228Pro	missense_variant	Exon 4 of 5	1	NM_024297.3	ENSP00000322579.3		Q9BUL5-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461158

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726846

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.030

T;.;.;.;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.87

D;D;D;D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.16

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;.;.;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.57

N;.;.;N;.

REVEL

Benign

0.15

Sift

Uncertain

0.0020

D;.;.;D;.

Sift4G

Benign

0.31

T;T;T;T;T

Polyphen

0.17

B;.;.;.;.

Vest4

0.40

MutPred

0.20

Loss of MoRF binding (P = 0.0322);.;.;.;.;

MVP

0.17

MPC

1.4

ClinPred

0.67

GERP RS

1.9

Varity_R

0.30

gMVP

0.56

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over