Genetic Variant PHF23:c.159+98T>C (chr17-7237287-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.42

Publications

36 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024297.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PHF23	NM_024297.3	MANE Select	c.159+98T>C	intron	N/A	NP_077273.2
PHF23	NM_001284518.2		c.147+98T>C	intron	N/A	NP_001271447.1
PHF23	NM_001284517.2		c.159+98T>C	intron	N/A	NP_001271446.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PHF23	ENST00000320316.8	TSL:1 MANE Select	c.159+98T>C	intron	N/A	ENSP00000322579.3
PHF23	ENST00000454255.6	TSL:2	c.147+98T>C	intron	N/A	ENSP00000414607.2
PHF23	ENST00000571362.5	TSL:2	c.159+98T>C	intron	N/A	ENSP00000460738.1

Frequencies

GnomAD3 genomes

AF:

0.480

AC:

72878

AN:

151750

Hom.:

18107

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.618

AC:

13114

AN:

21224

American (AMR)

AF:

0.516

AC:

15582

AN:

30202

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

7698

AN:

17778

East Asian (EAS)

AF:

0.654

AC:

23979

AN:

36670

South Asian (SAS)

AF:

0.389

AC:

24176

AN:

62202

European-Finnish (FIN)

AF:

0.389

AC:

18864

AN:

48450

Middle Eastern (MID)

AF:

0.368

AC:

1658

AN:

4502

European-Non Finnish (NFE)

AF:

0.418

AC:

270606

AN:

647516

Other (OTH)

AF:

0.449

AC:

18582

AN:

41386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

10777

21554

32330

43107

53884

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6878

13756

20634

27512

34390

<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:

0.480

AC:

72920

AN:

151868

Hom.:

18118

Cov.:

AF XY:

0.476

AC XY:

35319

AN XY:

74190

show subpopulations

African (AFR)

AF:

0.615

AC:

25458

AN:

41416

American (AMR)

AF:

0.468

AC:

7146

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

1539

AN:

3470

East Asian (EAS)

AF:

0.625

AC:

3230

AN:

5164

South Asian (SAS)

AF:

0.397

AC:

1912

AN:

4818

European-Finnish (FIN)

AF:

0.378

AC:

3967

AN:

10504

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.415

AC:

28198

AN:

67926

Other (OTH)

AF:

0.443

AC:

933

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1870

3740

5609

7479

9349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.442

Hom.:

11935

Bravo

AF:

0.498

Asia WGS

AF:

0.500

AC:

1737

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.43

(source)

DANN

Benign

0.57

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over