rs117616209

chr17-7239532-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The ENST00000570899.1(PHF23):c.46+54G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 386,856 control chromosomes in the GnomAD database, including 193 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 0.024 (69 hom., cov: 32)
  • Exomes 𝑓: 0.024 (124 hom.)
• Consequence: PHF23 ENST00000570899.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0238 (3591/151160) while in subpopulation NFE AF= 0.0366 (2475/67654). AF 95% confidence interval is 0.0354. There are 69 homozygotes in gnomad4. There are 1707 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 3592 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF23	XM_024450938.2	c.46+54G>A		intron_variant
PHF23	XM_047436728.1	c.46+54G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF23	ENST00000570899.1	c.46+54G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3592 AN: 151042 Hom.: 69 Cov.: 32

Gnomad AFR AF: 0.00661

Gnomad AMI AF: 0.0804

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0220

Gnomad FIN AF: 0.0225

Gnomad MID AF: 0.0484

Gnomad NFE AF: 0.0366

Gnomad OTH AF: 0.0294

GnomAD4 exome AF: 0.0240 AC: 5646 AN: 235696 Hom.: 124 Cov.: 0 AF XY: 0.0242 AC XY: 3053 AN XY: 126280

Gnomad4 AFR exome AF: 0.00537

Gnomad4 AMR exome AF: 0.0188

Gnomad4 ASJ exome AF: 0.0160

Gnomad4 EAS exome AF: 0.0000665

Gnomad4 SAS exome AF: 0.0225

Gnomad4 FIN exome AF: 0.0177

Gnomad4 NFE exome AF: 0.0288

Gnomad4 OTH exome AF: 0.0244

GnomAD4 genome AF: 0.0238 AC: 3591 AN: 151160 Hom.: 69 Cov.: 32 AF XY: 0.0231 AC XY: 1707 AN XY: 73892

Gnomad4 AFR AF: 0.00661

Gnomad4 AMR AF: 0.0198

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.0225

Gnomad4 NFE AF: 0.0366

Gnomad4 OTH AF: 0.0291

Alfa AF: 0.0288 Hom.: 12

Bravo AF: 0.0226

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
Cadd	Benign	14
Dann	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs117616209; hg19: chr17-7142851;