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GeneBe

14-72714445-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001280542.3(DPF3):c.582C>A(p.His194Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

DPF3
NM_001280542.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.59
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.06192586).
BS2
High AC in GnomAd at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DPF3NM_001280542.3 linkuse as main transcriptc.582C>A p.His194Gln missense_variant 6/11 ENST00000556509.6
DPF3NM_001280544.2 linkuse as main transcriptc.747C>A p.His249Gln missense_variant 6/10
DPF3NM_001280543.2 linkuse as main transcriptc.612C>A p.His204Gln missense_variant 7/11
DPF3NM_012074.5 linkuse as main transcriptc.582C>A p.His194Gln missense_variant 6/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DPF3ENST00000556509.6 linkuse as main transcriptc.582C>A p.His194Gln missense_variant 6/111 NM_001280542.3 P1Q92784-1

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152180
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000723
AC:
18
AN:
249112
Hom.:
0
AF XY:
0.0000666
AC XY:
9
AN XY:
135148
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:
0.000359
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.0000531
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000698
AC:
102
AN:
1461594
Hom.:
0
Cov.:
31
AF XY:
0.0000866
AC XY:
63
AN XY:
727092
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:
0.000197
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000720
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000919
AC:
14
AN:
152298
Hom.:
0
Cov.:
33
AF XY:
0.0000940
AC XY:
7
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000600
Hom.:
0
Bravo
AF:
0.0000453
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000119
AC:
1
ExAC
AF:
0.0000826
AC:
10
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsFeb 21, 2024The c.582C>A (p.H194Q) alteration is located in exon 6 (coding exon 6) of the DPF3 gene. This alteration results from a C to A substitution at nucleotide position 582, causing the histidine (H) at amino acid position 194 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
Benign
0.11
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.34
Cadd
Benign
0.64
Dann
Benign
0.89
DEOGEN2
Benign
0.015
T;T;.;.;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.034
N
LIST_S2
Benign
0.73
T;T;T;T;.
M_CAP
Benign
0.084
D
MetaRNN
Benign
0.062
T;T;T;T;T
MetaSVM
Benign
-0.47
T
MutationAssessor
Benign
0.92
L;.;L;.;.
MutationTaster
Benign
1.0
D;N;N;N
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-0.43
N;.;N;.;N
REVEL
Benign
0.16
Sift
Benign
0.20
T;.;T;.;T
Sift4G
Benign
0.58
T;T;T;T;T
Polyphen
0.0
B;.;P;.;.
Vest4
0.27
MutPred
0.15
Gain of catalytic residue at H194 (P = 0.1046);.;Gain of catalytic residue at H194 (P = 0.1046);.;.;
MVP
0.45
MPC
0.43
ClinPred
0.043
T
GERP RS
-9.8
Varity_R
0.046
gMVP
0.076

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.

Other links and lift over

dbSNP: rs200602274; hg19: chr14-73181153; COSMIC: COSV63502549; API