Variant 14-72693145-C-T 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.673G>A(p.Glu225Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,906 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

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

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

DPF3
NM_001280542.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

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:

DPF3 (HGNC:):

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	Protein	UniProt
DPF3	NM_001280542.3 linkuse as main transcript	c.673G>A	p.Glu225Lys	missense_variant	7/11	ENST00000556509.6	NP_001267471.1	Q92784-1
DPF3	NM_001280544.2 linkuse as main transcript	c.838G>A	p.Glu280Lys	missense_variant	7/10		NP_001267473.1	Q92784F8W7T1
DPF3	NM_001280543.2 linkuse as main transcript	c.703G>A	p.Glu235Lys	missense_variant	8/11		NP_001267472.1	Q92784-5
DPF3	NM_012074.5 linkuse as main transcript	c.673G>A	p.Glu225Lys	missense_variant	7/10		NP_036206.3	Q92784-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPF3	ENST00000556509.6 linkuse as main transcript	c.673G>A	p.Glu225Lys	missense_variant	7/11	1	NM_001280542.3	ENSP00000450518.1		Q92784-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249280

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135240

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461712

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

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

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Dec 03, 2024

The c.673G>A (p.E225K) alteration is located in exon 7 (coding exon 7) of the DPF3 gene. This alteration results from a G to A substitution at nucleotide position 673, causing the glutamic acid (E) at amino acid position 225 to be replaced by a lysine (K). 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

Uncertain

0.47

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.39

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

T;T;.;.;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.97

D;D;D;D;.

M_CAP

Uncertain

0.29

MetaRNN

Uncertain

0.73

D;D;D;D;D

MetaSVM

Pathogenic

0.85

MutationAssessor

Uncertain

2.6

M;.;M;.;.

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-2.4

N;.;D;.;D

REVEL

Uncertain

0.62

Sift

Benign

0.14

T;.;T;.;T

Sift4G

Benign

0.31

T;T;T;T;T

Polyphen

0.99

D;.;D;.;.

Vest4

0.74

MutPred

0.34

Gain of ubiquitination at E225 (P = 6e-04);.;Gain of ubiquitination at E225 (P = 6e-04);.;.;

MVP

0.96

MPC

1.1

ClinPred

0.90

GERP RS

5.5

Varity_R

0.29

gMVP

0.46

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