Genetic Variant PHF3:p.Gly233Arg (chr6-63684419-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001370348.2(PHF3):c.697G>A(p.Gly233Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00133 in 1,613,986 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0066 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 16 hom. )

Consequence

PHF3
NM_001370348.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.88

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023934245).

BP6

Variant 6-63684419-G-A is Benign according to our data. Variant chr6-63684419-G-A is described in ClinVar as Benign. ClinVar VariationId is 3041920.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0066 (1005/152260) while in subpopulation AFR AF = 0.0223 (926/41548). AF 95% confidence interval is 0.0211. There are 11 homozygotes in GnomAd4. There are 463 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 11 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370348.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHF3	NM_001370348.2	MANE Select	c.697G>A	p.Gly233Arg	missense	Exon 4 of 16	NP_001357277.1	Q92576-1
PHF3	NM_015153.4		c.697G>A	p.Gly233Arg	missense	Exon 3 of 15	NP_055968.1	Q92576-1
PHF3	NM_001290259.2		c.433G>A	p.Gly145Arg	missense	Exon 5 of 17	NP_001277188.1	Q92576-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHF3	ENST00000262043.8	TSL:5 MANE Select	c.697G>A	p.Gly233Arg	missense	Exon 4 of 16	ENSP00000262043.4	Q92576-1
PHF3	ENST00000393387.5	TSL:1	c.697G>A	p.Gly233Arg	missense	Exon 3 of 15	ENSP00000377048.1	Q92576-1
PHF3	ENST00000506783.5	TSL:1	c.139G>A	p.Gly47Arg	missense	Exon 2 of 12	ENSP00000424694.1	E7EVH3

Frequencies

GnomAD3 genomes

AF:

0.00659

AC:

1003

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0223

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00185

AC:

465

AN:

251262

AF XY:

0.00147

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.000781

AC:

1142

AN:

1461726

Hom.:

Cov.:

AF XY:

0.000710

AC XY:

516

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.0249

AC:

835

AN:

33470

American (AMR)

AF:

0.00197

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00225

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000872

AC:

AN:

1111894

Other (OTH)

AF:

0.00171

AC:

103

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

115

173

230

288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.00660

AC:

1005

AN:

152260

Hom.:

Cov.:

AF XY:

0.00622

AC XY:

463

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0223

AC:

926

AN:

41548

American (AMR)

AF:

0.00379

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68006

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

144

192

240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00256

Hom.:

Bravo

AF:

0.00744

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0232

AC:

102

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00203

AC:

246

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PHF3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.019

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.075

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0024

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

3.9

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.34

REVEL

Benign

0.080

Sift

Benign

0.097

Sift4G

Benign

0.50

Polyphen

0.22

Vest4

0.30

MutPred

0.097

Loss of sheet (P = 0.0457)

MVP

0.068

MPC

0.10

ClinPred

0.014

GERP RS

4.8

Varity_R

0.089

gMVP

0.12

Mutation Taster

=95/5

polymorphism

(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