NM_024297.3:c.997+11C>T

Variant names:

• chr17-7235919-G-A
• rs222851
• NM_024297.3:c.997+11C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
PHF23	NM_024297.3	c.997+11C>T		intron_variant	Intron 4 of 4	ENST00000320316.8	NP_077273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF23	ENST00000320316.8	c.997+11C>T		intron_variant	Intron 4 of 4	1	NM_024297.3	ENSP00000322579.3

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

GnomAD2 exomes AF: 0.423 AC: 104528 AN: 246890 AF XY: 0.411

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 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

African (AFR) AF: 0.599 AC: 20020 AN: 33418

American (AMR) AF: 0.499 AC: 22274 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 10784 AN: 25978

East Asian (EAS) AF: 0.652 AC: 25836 AN: 39606

South Asian (SAS) AF: 0.359 AC: 30944 AN: 86154

European-Finnish (FIN) AF: 0.366 AC: 19501 AN: 53342

Middle Eastern (MID) AF: 0.320 AC: 1839 AN: 5752

European-Non Finnish (NFE) AF: 0.387 AC: 429571 AN: 1108896

Other (OTH) AF: 0.421 AC: 25329 AN: 60228

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

African (AFR) AF: 0.591 AC: 24514 AN: 41486

American (AMR) AF: 0.445 AC: 6802 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1487 AN: 3472

East Asian (EAS) AF: 0.627 AC: 3245 AN: 5178

South Asian (SAS) AF: 0.371 AC: 1789 AN: 4822

European-Finnish (FIN) AF: 0.357 AC: 3778 AN: 10584

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25745 AN: 67976

Other (OTH) AF: 0.410 AC: 866 AN: 2110

Alfa AF: 0.393 Hom.: 11270

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
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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