Genetic Variant PHF23:c.46+54G>A (chr17-7239532-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00800

Publications

12 publications found

Variant links:

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]

PHF23 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 3591 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
PHF23	XM_024450938.2 link	c.46+54G>A	intron_variant	Intron 1 of 4		XP_024306706.1
PHF23	XM_047436728.1 link	c.46+54G>A	intron_variant	Intron 1 of 4		XP_047292684.1
PHF23	NM_024297.3 link	c.-253G>A	upstream_gene_variant		ENST00000320316.8	NP_077273.2
PHF23	NM_001284517.2 link	c.-253G>A	upstream_gene_variant			NP_001271446.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
PHF23	ENST00000570899.1 link	c.46+54G>A	intron_variant	Intron 1 of 3	3		ENSP00000458416.1
PHF23	ENST00000320316.8 link	c.-253G>A	upstream_gene_variant		1	NM_024297.3	ENSP00000322579.3
PHF23	ENST00000571362.5 link	c.-253G>A	upstream_gene_variant		2		ENSP00000460738.1
PHF23	ENST00000576955.5 link	c.-611G>A	upstream_gene_variant		2		ENSP00000458953.1

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3592

AN:

151042

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0242

AC XY:

3053

AN XY:

126280

show subpopulations

African (AFR)

AF:

0.00537

AC:

AN:

5028

American (AMR)

AF:

0.0188

AC:

132

AN:

7032

Ashkenazi Jewish (ASJ)

AF:

0.0160

AC:

116

AN:

7248

East Asian (EAS)

AF:

0.0000665

AC:

AN:

15040

South Asian (SAS)

AF:

0.0225

AC:

651

AN:

28898

European-Finnish (FIN)

AF:

0.0177

AC:

307

AN:

17342

Middle Eastern (MID)

AF:

0.0370

AC:

AN:

1026

European-Non Finnish (NFE)

AF:

0.0288

AC:

4040

AN:

140368

Other (OTH)

AF:

0.0244

AC:

334

AN:

13714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

276

552

829

1105

1381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0238

AC:

3591

AN:

151160

Hom.:

Cov.:

AF XY:

0.0231

AC XY:

1707

AN XY:

73892

show subpopulations

African (AFR)

AF:

0.00661

AC:

272

AN:

41120

American (AMR)

AF:

0.0198

AC:

302

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5080

South Asian (SAS)

AF:

0.0220

AC:

105

AN:

4766

European-Finnish (FIN)

AF:

0.0225

AC:

238

AN:

10570

Middle Eastern (MID)

AF:

0.0486

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0366

AC:

2475

AN:

67654

Other (OTH)

AF:

0.0291

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

174

348

523

697

871

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0288

Hom.:

Bravo

AF:

0.0226

Asia WGS

AF:

0.0140

AC:

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

(source)

DANN

Benign

0.89

PhyloP100

0.0080

PromoterAI

0.11

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over