Variant 14-72723634-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001280542.3(DPF3):c.524G>A(p.Arg175Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000831 in 1,563,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

DPF3
NM_001280542.3 missense, splice_region

Scores

Splicing: ADA: 0.02381

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.72

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.39361507).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPF3	NM_001280542.3 linkuse as main transcript	c.524G>A	p.Arg175Gln	missense_variant, splice_region_variant	5/11	ENST00000556509.6	NP_001267471.1	Q92784-1
DPF3	NM_001280544.2 linkuse as main transcript	c.689G>A	p.Arg230Gln	missense_variant, splice_region_variant	5/10		NP_001267473.1	Q92784F8W7T1
DPF3	NM_001280543.2 linkuse as main transcript	c.554G>A	p.Arg185Gln	missense_variant, splice_region_variant	6/11		NP_001267472.1	Q92784-5
DPF3	NM_012074.5 linkuse as main transcript	c.524G>A	p.Arg175Gln	missense_variant, splice_region_variant	5/10		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.524G>A	p.Arg175Gln	missense_variant, splice_region_variant	5/11	1	NM_001280542.3	ENSP00000450518.1		Q92784-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000497

AC:

AN:

201118

Hom.:

AF XY:

0.00000905

AC XY:

AN XY:

110482

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000567

AC:

AN:

1411854

Hom.:

Cov.:

AF XY:

0.00000570

AC XY:

AN XY:

701500

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000730

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

Nov 10, 2024

The c.524G>A (p.R175Q) alteration is located in exon 5 (coding exon 5) of the DPF3 gene. This alteration results from a G to A substitution at nucleotide position 524, causing the arginine (R) at amino acid position 175 to be replaced by a glutamine (Q). 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

0.56

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.061

T;T;.;.;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D;D;D;.

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.39

T;T;T;T;T

MetaSVM

Uncertain

0.64

MutationAssessor

Uncertain

2.3

M;.;M;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.9

N;.;N;.;N

REVEL

Uncertain

0.41

Sift

Benign

0.086

T;.;D;.;T

Sift4G

Uncertain

0.024

D;D;D;D;D

Polyphen

0.14

B;.;D;.;.

Vest4

0.46

MutPred

0.28

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

MVP

0.72

MPC

1.1

ClinPred

0.83

GERP RS

4.2

Varity_R

0.19

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.024

dbscSNV1_RF

Benign

0.36

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