chr17-7236140-C-A

Variant names:

• chr17-7236140-C-A
• rs778544557
• NM_024297.3:c.787G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024297.3(PHF23):​c.787G>T​(p.Ala263Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. A263T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PHF23 NM_024297.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042861313).

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.787G>T	p.Ala263Ser	missense	Exon 4 of 5	NP_077273.2	Q9BUL5-1
	PHF23	NM_001284518.2		c.775G>T	p.Ala259Ser	missense	Exon 4 of 5	NP_001271447.1	Q9BUL5-4
	PHF23	NM_001284517.2		c.586G>T	p.Ala196Ser	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.787G>T	p.Ala263Ser	missense	Exon 4 of 5	ENSP00000322579.3	Q9BUL5-1
	PHF23	ENST00000454255.6	TSL:2	c.775G>T	p.Ala259Ser	missense	Exon 4 of 5	ENSP00000414607.2	Q9BUL5-4
	PHF23	ENST00000571362.5	TSL:2	c.586G>T	p.Ala196Ser	missense	Exon 4 of 5	ENSP00000460738.1	Q9BUL5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458190 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 725220

African (AFR) AF: 0.00 AC: 0 AN: 33408

American (AMR) AF: 0.00 AC: 0 AN: 44376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25716

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 85644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110168

Other (OTH) AF: 0.00 AC: 0 AN: 60240

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.5
DANN	Benign	0.93
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.0020
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.013
Sift	Benign	0.42	T
Sift4G	Benign	0.84	T
Polyphen		0.0	B
Vest4		0.087
MutPred		0.13		Gain of phosphorylation at A263 (P = 0.0039)
MVP		0.043
MPC		0.33
ClinPred		0.055	T
GERP RS		0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.045
gMVP		0.11

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

Other links and lift over

dbSNP: rs778544557; hg19: chr17-7139459;