Variant 6-63684419-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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

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 made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF3	NM_001370348.2 link	c.697G>A	p.Gly233Arg	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.697G>A	p.Gly233Arg	missense_variant	Exon 4 of 16	5	NM_001370348.2	ENSP00000262043.4		Q92576-1

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

GnomAD3 exomes

AF:

0.00185

AC:

465

AN:

251262

Hom.:

AF XY:

0.00147

AC XY:

199

AN XY:

135798

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 SAS exome

AF:

0.0000327

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

Gnomad4 AFR exome

AF:

0.0249

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000872

Gnomad4 OTH exome

AF:

0.00171

GnomAD4 genome

AF:

0.00660

AC:

1005

AN:

152260

Hom.:

Cov.:

AF XY:

0.00622

AC XY:

463

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0223

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00132

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

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PHF3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 15, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.019

.;T;T;T;.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.075

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.84

T;T;T;.;T;T

MetaRNN

Benign

0.0024

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;.;.;L;.;L

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.34

N;N;N;N;N;N

REVEL

Benign

0.080

Sift

Benign

0.097

T;T;T;T;T;T

Sift4G

Benign

0.50

T;T;T;T;T;T

Polyphen

0.22, 0.62

.;.;.;B;P;B

Vest4

0.30, 0.15, 0.34

MutPred

0.097

.;.;.;Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over