17-7236206-G-A

Variant names:

• chr17-7236206-G-A
• NM_024297.3:c.721C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_024297.3(PHF23):​c.721C>T​(p.Pro241Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,460,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.0000082 (0 hom.)
• Consequence: PHF23 NM_024297.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.76
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11722562).
• BS2: High AC in GnomAdExome4 at 12 AD gene.

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.721C>T	p.Pro241Ser	missense	Exon 4 of 5	NP_077273.2	Q9BUL5-1
	PHF23	NM_001284518.2		c.709C>T	p.Pro237Ser	missense	Exon 4 of 5	NP_001271447.1	Q9BUL5-4
	PHF23	NM_001284517.2		c.520C>T	p.Pro174Ser	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.721C>T	p.Pro241Ser	missense	Exon 4 of 5	ENSP00000322579.3	Q9BUL5-1
	PHF23	ENST00000454255.6	TSL:2	c.709C>T	p.Pro237Ser	missense	Exon 4 of 5	ENSP00000414607.2	Q9BUL5-4
	PHF23	ENST00000571362.5	TSL:2	c.520C>T	p.Pro174Ser	missense	Exon 4 of 5	ENSP00000460738.1	Q9BUL5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000822 AC: 12 AN: 1460500 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 726476

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1111330

Other (OTH) AF: 0.0000331 AC: 2 AN: 60332

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	0.094
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.085
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.8
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.086
Sift	Benign	0.030	D
Sift4G	Benign	0.61	T
Polyphen		0.0030	B
Vest4		0.15
MutPred		0.34		Gain of phosphorylation at P241 (P = 4e-04)
MVP		0.082
MPC		0.47
ClinPred		0.21	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.077
gMVP		0.43
Mutation Taster		=88/12	polymorphism

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

hg19: chr17-7139525;