chr17-7236736-G-T

Position:

• chr17-7236736-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024297.3(PHF23):​c.191C>A​(p.Ser64Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S64T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHF23 NM_024297.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.42

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF23	NM_024297.3	c.191C>A	p.Ser64Tyr	missense_variant	4/5	ENST00000320316.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF23	ENST00000320316.8	c.191C>A	p.Ser64Tyr	missense_variant	4/5	1	NM_024297.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2023

The c.191C>A (p.S64Y) alteration is located in exon 4 (coding exon 4) of the PHF23 gene. This alteration results from a C to A substitution at nucleotide position 191, causing the serine (S) at amino acid position 64 to be replaced by a tyrosine (Y). 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	0.65
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T;.;T;T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.46	T;T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.9	L;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.5	D;D;.;.;.
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D;D;.;.;.
Sift4G	Uncertain	0.0030	D;D;D;.;D
Polyphen		0.99	D;.;.;.;.
Vest4		0.49
MutPred		0.22		Loss of glycosylation at S64 (P = 0.0065);.;Loss of glycosylation at S64 (P = 0.0065);.;.;
MVP		0.10
MPC		1.3
ClinPred		0.98	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.84
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7140055;