Variant 6-63684176-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001370348.2(PHF3):c.454G>T(p.Ala152Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000951 in 1,613,528 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 8 hom. )

Consequence

PHF3
NM_001370348.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.262

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031266212).

BP6

Variant 6-63684176-G-T is Benign according to our data. Variant chr6-63684176-G-T is described in ClinVar as [Benign]. Clinvar id is 716135.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00487 (741/152164) while in subpopulation AFR AF= 0.017 (704/41526). AF 95% confidence interval is 0.0159. There are 6 homozygotes in gnomad4. There are 349 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF3	NM_001370348.2 linkuse as main transcript	c.454G>T	p.Ala152Ser	missense_variant	4/16	ENST00000262043.8	NP_001357277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF3	ENST00000262043.8 linkuse as main transcript	c.454G>T	p.Ala152Ser	missense_variant	4/16	5	NM_001370348.2	ENSP00000262043.4		Q92576-1

Frequencies

GnomAD3 genomes

AF:

0.00488

AC:

742

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00481

GnomAD3 exomes

AF:

0.00129

AC:

324

AN:

250746

Hom.:

AF XY:

0.000966

AC XY:

131

AN XY:

135546

show subpopulations

Gnomad AFR exome

AF:

0.0170

Gnomad AMR exome

AF:

0.000956

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000882

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000543

AC:

794

AN:

1461364

Hom.:

Cov.:

AF XY:

0.000466

AC XY:

339

AN XY:

726980

show subpopulations

Gnomad4 AFR exome

AF:

0.0188

Gnomad4 AMR exome

AF:

0.000941

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.00487

AC:

741

AN:

152164

Hom.:

Cov.:

AF XY:

0.00469

AC XY:

349

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0170

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00476

Alfa

AF:

0.000649

Hom.:

Bravo

AF:

0.00534

ESP6500AA

AF:

0.0170

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00171

AC:

208

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 27, 2018

- -

PHF3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 06, 2019

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

0.084

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.020

T;T;T;.;T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.72

T;T;.;T;T;T

MetaRNN

Benign

0.0031

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;.;N;.;N;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.32

N;N;N;N;N;N

REVEL

Benign

0.031

Sift

Uncertain

0.0020

D;D;D;D;D;D

Sift4G

Benign

0.14

T;T;T;T;T;T

Polyphen

0.38, 0.65

.;.;B;P;B;.

Vest4

0.18, 0.066

MVP

0.093

MPC

0.070

ClinPred

0.035

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.097

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