chr17-7236239-C-A

Variant names:

• chr17-7236239-C-A
• rs1452527826
• NM_024297.3:c.688G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024297.3(PHF23):​c.688G>T​(p.Asp230Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PHF23 NM_024297.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13430068).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024297.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF23	NM_024297.3	MANE Select	c.688G>T	p.Asp230Tyr	missense	Exon 4 of 5	NP_077273.2	Q9BUL5-1
	PHF23	NM_001284518.2		c.676G>T	p.Asp226Tyr	missense	Exon 4 of 5	NP_001271447.1	Q9BUL5-4
	PHF23	NM_001284517.2		c.487G>T	p.Asp163Tyr	missense	Exon 4 of 5	NP_001271446.1	Q9BUL5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF23	ENST00000320316.8	TSL:1 MANE Select	c.688G>T	p.Asp230Tyr	missense	Exon 4 of 5	ENSP00000322579.3	Q9BUL5-1
	PHF23	ENST00000454255.6	TSL:2	c.676G>T	p.Asp226Tyr	missense	Exon 4 of 5	ENSP00000414607.2	Q9BUL5-4
	PHF23	ENST00000571362.5	TSL:2	c.487G>T	p.Asp163Tyr	missense	Exon 4 of 5	ENSP00000460738.1	Q9BUL5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248242 AF XY: 0.00

Gnomad AFR exome AF: 0.0000648

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460818 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726644

African (AFR) AF: 0.0000299 AC: 1 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26034

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111468

Other (OTH) AF: 0.00 AC: 0 AN: 60344

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.046
FATHMM_MKL	Benign	0.29	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.8
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.063
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.078	T
Polyphen		0.028	B
Vest4		0.24
MutPred		0.21		Gain of phosphorylation at D230 (P = 0.0013)
MVP		0.11
MPC		1.3
ClinPred		0.33	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1452527826; hg19: chr17-7139558;