rs222852

Positions:

• chr17-7237287-A-G
• chr17-7237287-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024297.3(PHF23):​c.159+98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,061,798 control chromosomes in the GnomAD database, including 106,332 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (18118 hom., cov: 31)
  • Exomes 𝑓: 0.43 (88214 hom.)
• Consequence: PHF23 NM_024297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF23	NM_024297.3	c.159+98T>C		intron_variant		ENST00000320316.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF23	ENST00000320316.8	c.159+98T>C		intron_variant		1	NM_024297.3	P1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72878 AN: 151750 Hom.: 18107 Cov.: 31

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.449

GnomAD4 exome AF: 0.433 AC: 394259 AN: 909930 Hom.: 88214 AF XY: 0.429 AC XY: 199210 AN XY: 464410

Gnomad4 AFR exome AF: 0.618

Gnomad4 AMR exome AF: 0.516

Gnomad4 ASJ exome AF: 0.433

Gnomad4 EAS exome AF: 0.654

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.389

Gnomad4 NFE exome AF: 0.418

Gnomad4 OTH exome AF: 0.449

GnomAD4 genome AF: 0.480 AC: 72920 AN: 151868 Hom.: 18118 Cov.: 31 AF XY: 0.476 AC XY: 35319 AN XY: 74190

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.443

Alfa AF: 0.432 Hom.: 8151

Bravo AF: 0.498

Asia WGS AF: 0.500 AC: 1737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.57

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

LitVar

Other links and lift over

dbSNP: rs222852; hg19: chr17-7140606; COSMIC: COSV50035883; COSMIC: COSV50035883;