Genetic Variant DPF3:p.Glu226Val (chr14-72693141-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPF3	NM_001280542.3 link	c.677A>T	p.Glu226Val	missense_variant	Exon 7 of 11	ENST00000556509.6	NP_001267471.1	Q92784-1
DPF3	NM_001280544.2 link	c.842A>T	p.Glu281Val	missense_variant	Exon 7 of 10		NP_001267473.1	Q92784F8W7T1
DPF3	NM_001280543.2 link	c.707A>T	p.Glu236Val	missense_variant	Exon 8 of 11		NP_001267472.1	Q92784-5
DPF3	NM_012074.5 link	c.677A>T	p.Glu226Val	missense_variant	Exon 7 of 10		NP_036206.3	Q92784-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPF3	ENST00000556509.6 link	c.677A>T	p.Glu226Val	missense_variant	Exon 7 of 11	1	NM_001280542.3	ENSP00000450518.1		Q92784-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249290

AF XY:

0.00000739

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 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

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111868

Other (OTH)

AF:

0.00

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

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

Jan 09, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

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;.;.

PhyloP100

7.7

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

Mutation Taster

=48/52

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over