chr14-72723634-C-T
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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. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000057 ( 0 hom. )
Consequence
DPF3
NM_001280542.3 missense, splice_region
NM_001280542.3 missense, splice_region
Scores
2
12
5
Splicing: ADA: 0.02381
2
Clinical Significance
Conservation
PhyloP100: 5.72
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 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 | c.524G>A | p.Arg175Gln | missense_variant, splice_region_variant | 5/11 | ENST00000556509.6 | NP_001267471.1 | |
DPF3 | NM_001280544.2 | c.689G>A | p.Arg230Gln | missense_variant, splice_region_variant | 5/10 | NP_001267473.1 | ||
DPF3 | NM_001280543.2 | c.554G>A | p.Arg185Gln | missense_variant, splice_region_variant | 6/11 | NP_001267472.1 | ||
DPF3 | NM_012074.5 | c.524G>A | p.Arg175Gln | missense_variant, splice_region_variant | 5/10 | NP_036206.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152092Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000497 AC: 1AN: 201118Hom.: 0 AF XY: 0.00000905 AC XY: 1AN XY: 110482
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GnomAD4 exome AF: 0.00000567 AC: 8AN: 1411854Hom.: 0 Cov.: 30 AF XY: 0.00000570 AC XY: 4AN XY: 701500
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152092Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74280
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;.
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;M;.;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;.;N
REVEL
Uncertain
Sift
Benign
T;.;D;.;T
Sift4G
Uncertain
D;D;D;D;D
Polyphen
B;.;D;.;.
Vest4
MutPred
Loss of methylation at R175 (P = 0.0011);.;Loss of methylation at R175 (P = 0.0011);.;.;
MVP
MPC
1.1
ClinPred
D
GERP RS
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gMVP
Splicing
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Calibrated prediction
Score
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at