Variant 14-72693141-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001280542.3(DPF3):c.677A>T(p.Glu226Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DPF3
NM_001280542.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DPF3	NM_001280542.3 linkuse as main transcript	c.677A>T	p.Glu226Val	missense_variant	7/11	ENST00000556509.6
DPF3	NM_001280544.2 linkuse as main transcript	c.842A>T	p.Glu281Val	missense_variant	7/10
DPF3	NM_001280543.2 linkuse as main transcript	c.707A>T	p.Glu236Val	missense_variant	8/11
DPF3	NM_012074.5 linkuse as main transcript	c.677A>T	p.Glu226Val	missense_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPF3	ENST00000556509.6 linkuse as main transcript	c.677A>T	p.Glu226Val	missense_variant	7/11	1	NM_001280542.3	P1	Q92784-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249290

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135246

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00000138

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:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 09, 2024

The c.677A>T (p.E226V) alteration is located in exon 7 (coding exon 7) of the DPF3 gene. This alteration results from a A to T substitution at nucleotide position 677, causing the glutamic acid (E) at amino acid position 226 to be replaced by a valine (V). 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

0.61

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.40

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Benign

0.21

T;T;.;.;.

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.84

T;T;T;T;.

M_CAP

Pathogenic

0.46

MetaRNN

Uncertain

0.70

D;D;D;D;D

MetaSVM

Pathogenic

0.86

MutationAssessor

Uncertain

2.6

M;.;M;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-3.6

D;.;D;.;D

REVEL

Pathogenic

0.70

Sift

Benign

0.046

D;.;D;.;D

Sift4G

Benign

0.075

T;D;T;T;T

Polyphen

0.98

D;.;D;.;.

Vest4

0.63

MutPred

0.16

Loss of disorder (P = 0.0714);.;Loss of disorder (P = 0.0714);.;.;

MVP

0.94

MPC

1.2

ClinPred

0.97

GERP RS

5.5

Varity_R

0.25

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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