Genetic Variant PHF3:p.Lys148Arg (chr6-63684165-A-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001370348.2(PHF3):c.443A>G(p.Lys148Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00866 in 1,612,520 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0087 ( 90 hom. )

Consequence

PHF3
NM_001370348.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.43

Publications

13 publications found

Variant links:

Genes affected

PHF3 (HGNC:8921): (PHD finger protein 3) This gene encodes a member of a PHD finger-containing gene family. This gene may function as a transcription factor and may be involved in glioblastomas development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

PHF3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066666007).

BP6

Variant 6-63684165-A-G is Benign according to our data. Variant chr6-63684165-A-G is described in ClinVar as [Benign]. Clinvar id is 781871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF3	NM_001370348.2 link	c.443A>G	p.Lys148Arg	missense_variant	Exon 4 of 16	ENST00000262043.8	NP_001357277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF3	ENST00000262043.8 link	c.443A>G	p.Lys148Arg	missense_variant	Exon 4 of 16	5	NM_001370348.2	ENSP00000262043.4		Q92576-1

Frequencies

GnomAD3 genomes

AF:

0.00845

AC:

1286

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.0360

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0338

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00941

Gnomad OTH

AF:

0.00959

GnomAD2 exomes

AF:

0.00951

AC:

2374

AN:

249728

AF XY:

0.00930

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00324

Gnomad ASJ exome

AF:

0.0382

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0311

Gnomad NFE exome

AF:

0.00875

Gnomad OTH exome

AF:

0.00973

GnomAD4 exome

AF:

0.00868

AC:

12675

AN:

1460250

Hom.:

Cov.:

AF XY:

0.00867

AC XY:

6297

AN XY:

726392

show subpopulations

African (AFR)

AF:

0.00168

AC:

AN:

33348

American (AMR)

AF:

0.00327

AC:

145

AN:

44410

Ashkenazi Jewish (ASJ)

AF:

0.0364

AC:

946

AN:

26008

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00448

AC:

385

AN:

85930

European-Finnish (FIN)

AF:

0.0305

AC:

1630

AN:

53360

Middle Eastern (MID)

AF:

0.0158

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00789

AC:

8766

AN:

1111436

Other (OTH)

AF:

0.0109

AC:

656

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

611

1222

1832

2443

3054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00845

AC:

1287

AN:

152270

Hom.:

Cov.:

AF XY:

0.00925

AC XY:

689

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

41564

American (AMR)

AF:

0.00288

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0360

AC:

125

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00290

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0338

AC:

359

AN:

10608

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00941

AC:

640

AN:

68000

Other (OTH)

AF:

0.00949

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

118

176

235

294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00873

Hom.:

Bravo

AF:

0.00538

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00942

AC:

ExAC

AF:

0.00932

AC:

1132

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00797

EpiControl

AF:

0.00889

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PHF3: BS1, BS2 -

Jun 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

T;T;T;.;T;.

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.86

D;D;.;D;D;T

MetaRNN

Benign

0.0067

T;T;T;T;T;T

MetaSVM

Benign

-0.52

MutationAssessor

Benign

0.55

.;.;N;.;N;.

PhyloP100

4.4

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.0

N;N;N;N;N;D

REVEL

Benign

0.18

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Uncertain

0.047

D;T;T;T;T;D

Polyphen

1.0

.;.;D;D;D;.

Vest4

0.46, 0.26, 0.61

MVP

0.56

MPC

0.30

ClinPred

0.036

GERP RS

5.9

Varity_R

0.33

gMVP

0.18

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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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6-63684165-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over