rs222851

Positions:

• chr17-7235919-G-A

Variant summary

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

The NM_024297.3(PHF23):​c.997+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,610,124 control chromosomes in the GnomAD database, including 137,148 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 0.45 (16233 hom., cov: 33)
  • Exomes 𝑓: 0.40 (120915 hom.)
• Consequence: PHF23 NM_024297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF23	NM_024297.3	c.997+11C>T		intron_variant		ENST00000320316.8	NP_077273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF23	ENST00000320316.8	c.997+11C>T		intron_variant		1	NM_024297.3	ENSP00000322579	P1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68635 AN: 152000 Hom.: 16225 Cov.: 33

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.416

GnomAD3 exomes AF: 0.423 AC: 104528 AN: 246890 Hom.: 23417 AF XY: 0.411 AC XY: 55131 AN XY: 134104

Gnomad AFR exome AF: 0.598

Gnomad AMR exome AF: 0.508

Gnomad ASJ exome AF: 0.419

Gnomad EAS exome AF: 0.623

Gnomad SAS exome AF: 0.357

Gnomad FIN exome AF: 0.359

Gnomad NFE exome AF: 0.373

Gnomad OTH exome AF: 0.401

GnomAD4 exome AF: 0.402 AC: 586098 AN: 1458006 Hom.: 120915 Cov.: 48 AF XY: 0.398 AC XY: 288528 AN XY: 724506

Gnomad4 AFR exome AF: 0.599

Gnomad4 AMR exome AF: 0.499

Gnomad4 ASJ exome AF: 0.415

Gnomad4 EAS exome AF: 0.652

Gnomad4 SAS exome AF: 0.359

Gnomad4 FIN exome AF: 0.366

Gnomad4 NFE exome AF: 0.387

Gnomad4 OTH exome AF: 0.421

GnomAD4 genome AF: 0.451 AC: 68676 AN: 152118 Hom.: 16233 Cov.: 33 AF XY: 0.448 AC XY: 33317 AN XY: 74358

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.410

Alfa AF: 0.392 Hom.: 8272

Bravo AF: 0.469

Asia WGS AF: 0.481 AC: 1671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.85

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: rs222851; hg19: chr17-7139238; COSMIC: COSV50036671; COSMIC: COSV50036671;