Genetic Variant PHF19:c.*1993T>C (chr9-120855951-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_015651.3(PHF19):c.*1993T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,572 control chromosomes in the GnomAD database, including 41,560 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 0.74 ( 41453 hom., cov: 31)

Exomes 𝑓: 0.67 ( 107 hom. )

Consequence

PHF19
NM_015651.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.517

Publications

26 publications found

Variant links:

Genes affected

PHF19 (HGNC:24566): (PHD finger protein 19) Enables methylated histone binding activity. Involved in positive regulation of histone H3-K27 methylation. Colocalizes with ESC/E(Z) complex. [provided by Alliance of Genome Resources, Apr 2022]

PHF19 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=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015651.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PHF19	NM_015651.3	MANE Select	c.*1993T>C	3_prime_UTR	Exon 15 of 15	NP_056466.1
PHF19	NR_104601.1		n.3138T>C	non_coding_transcript_exon	Exon 9 of 9
PHF19	NM_001286840.1		c.*1993T>C	3_prime_UTR	Exon 15 of 15	NP_001273769.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PHF19	ENST00000373896.8	TSL:2 MANE Select	c.*1993T>C	3_prime_UTR	Exon 15 of 15	ENSP00000363003.3
PHF19	ENST00000616568.5	TSL:1	c.*1993T>C	3_prime_UTR	Exon 15 of 15	ENSP00000483946.1
PHF19	ENST00000419155.5	TSL:2	c.*1993T>C	3_prime_UTR	Exon 10 of 10	ENSP00000407433.1

Frequencies

GnomAD3 genomes

AF:

0.736

AC:

111904

AN:

151974

Hom.:

41407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.746

Gnomad AMI

AF:

0.692

Gnomad AMR

AF:

0.822

Gnomad ASJ

AF:

0.783

Gnomad EAS

AF:

0.566

Gnomad SAS

AF:

0.796

Gnomad FIN

AF:

0.687

Gnomad MID

AF:

0.803

Gnomad NFE

AF:

0.725

Gnomad OTH

AF:

0.758

GnomAD4 exome

AF:

0.669

AC:

321

AN:

480

Hom.:

107

Cov.:

AF XY:

0.694

AC XY:

204

AN XY:

294

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.658

AC:

283

AN:

430

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.738

AC:

AN:

Other (OTH)

AF:

0.833

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.736

AC:

112000

AN:

152092

Hom.:

41453

Cov.:

AF XY:

0.738

AC XY:

54851

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.746

AC:

30926

AN:

41468

American (AMR)

AF:

0.823

AC:

12583

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.783

AC:

2719

AN:

3472

East Asian (EAS)

AF:

0.565

AC:

2914

AN:

5158

South Asian (SAS)

AF:

0.797

AC:

3836

AN:

4812

European-Finnish (FIN)

AF:

0.687

AC:

7279

AN:

10590

Middle Eastern (MID)

AF:

0.795

AC:

232

AN:

292

European-Non Finnish (NFE)

AF:

0.725

AC:

49277

AN:

67976

Other (OTH)

AF:

0.758

AC:

1603

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1505

3009

4514

6018

7523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

850

1700

2550

3400

4250

<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:

0.740

Hom.:

51513

Bravo

AF:

0.746

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.28

(source)

DANN

Benign

0.42

PhyloP100

-0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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