Variant 14-72723635-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001280542.3(DPF3):c.523C>T(p.Arg175Trp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000704 in 1,561,700 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

DPF3
NM_001280542.3 missense, splice_region

Scores

Splicing: ADA: 0.9744

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.25

Variant links:

Genes affected

DPF3 (HGNC:17427): (double PHD fingers 3) This gene encodes a member of the D4 protein family. The encoded protein is a transcription regulator that binds acetylated histones and is a component of the BAF chromatin remodeling complex. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

DPF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DPF3	NM_001280542.3 linkuse as main transcript	c.523C>T	p.Arg175Trp	missense_variant, splice_region_variant	5/11	ENST00000556509.6
DPF3	NM_001280544.2 linkuse as main transcript	c.688C>T	p.Arg230Trp	missense_variant, splice_region_variant	5/10
DPF3	NM_001280543.2 linkuse as main transcript	c.553C>T	p.Arg185Trp	missense_variant, splice_region_variant	6/11
DPF3	NM_012074.5 linkuse as main transcript	c.523C>T	p.Arg175Trp	missense_variant, splice_region_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPF3	ENST00000556509.6 linkuse as main transcript	c.523C>T	p.Arg175Trp	missense_variant, splice_region_variant	5/11	1	NM_001280542.3	P1	Q92784-1

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151446

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000709

AC:

AN:

1410254

Hom.:

Cov.:

AF XY:

0.0000128

AC XY:

AN XY:

700658

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000322

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000822

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151446

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73884

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000659

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 21, 2023

The c.523C>T (p.R175W) alteration is located in exon 5 (coding exon 5) of the DPF3 gene. This alteration results from a C to T substitution at nucleotide position 523, causing the arginine (R) at amino acid position 175 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.34

T;T;.;.;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.97

D;D;D;D;.

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.51

D;D;D;D;D

MetaSVM

Uncertain

0.76

MutationAssessor

Uncertain

2.3

M;.;M;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-4.9

D;.;D;.;D

REVEL

Uncertain

0.48

Sift

Uncertain

0.0010

D;.;D;.;D

Sift4G

Uncertain

0.0020

D;D;D;D;D

Polyphen

1.0

D;.;D;.;.

Vest4

0.52

MutPred

0.32

Loss of methylation at R175 (P = 0.0011);.;Loss of methylation at R175 (P = 0.0011);.;.;

MVP

0.71

MPC

1.2

ClinPred

1.0

GERP RS

5.1

Varity_R

0.29

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.97

dbscSNV1_RF

Benign

0.58

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