chr17-7236737-A-T

Position:

• chr17-7236737-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024297.3(PHF23):​c.190T>A​(p.Ser64Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. S64Y) 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: 2.17

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19913235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF23	NM_024297.3	c.190T>A	p.Ser64Thr	missense_variant	4/5	ENST00000320316.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF23	ENST00000320316.8	c.190T>A	p.Ser64Thr	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.190T>A (p.S64T) alteration is located in exon 4 (coding exon 4) of the PHF23 gene. This alteration results from a T to A substitution at nucleotide position 190, causing the serine (S) at amino acid position 64 to be replaced by a threonine (T). 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	0.19
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T;.;T;T;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.68	T;T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.20	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L;.;.;.;.
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.7	N;N;.;.;.
REVEL	Benign	0.11
Sift	Uncertain	0.0060	D;D;.;.;.
Sift4G	Uncertain	0.024	D;D;D;.;D
Polyphen		0.98	D;.;.;.;.
Vest4		0.37
MutPred		0.15		Loss of glycosylation at S64 (P = 0.0582);.;Loss of glycosylation at S64 (P = 0.0582);.;.;
MVP		0.11
MPC		0.75
ClinPred		0.79	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.35
gMVP		0.41

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: chr17-7140056;