14-72674356-G-A
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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.755C>T(p.Pro252Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,612,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
DPF3
NM_001280542.3 missense
NM_001280542.3 missense
Scores
5
9
5
Clinical Significance
Conservation
PhyloP100: 8.13
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=0.40958542).
BS2
High AC in GnomAdExome4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DPF3 | NM_001280542.3 | c.755C>T | p.Pro252Leu | missense_variant | 8/11 | ENST00000556509.6 | |
DPF3 | NM_001280544.2 | c.920C>T | p.Pro307Leu | missense_variant | 8/10 | ||
DPF3 | NM_001280543.2 | c.785C>T | p.Pro262Leu | missense_variant | 9/11 | ||
DPF3 | NM_012074.5 | c.755C>T | p.Pro252Leu | missense_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DPF3 | ENST00000556509.6 | c.755C>T | p.Pro252Leu | missense_variant | 8/11 | 1 | NM_001280542.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000198 AC: 3AN: 151888Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000811 AC: 2AN: 246610Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133662
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GnomAD4 exome AF: 0.00000959 AC: 14AN: 1460514Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7AN XY: 726336
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GnomAD4 genome AF: 0.0000198 AC: 3AN: 151888Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74158
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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 | Mar 01, 2023 | The c.755C>T (p.P252L) alteration is located in exon 8 (coding exon 8) of the DPF3 gene. This alteration results from a C to T substitution at nucleotide position 755, causing the proline (P) at amino acid position 252 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.;.
Eigen
Uncertain
Eigen_PC
Pathogenic
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;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;D;.;D
REVEL
Uncertain
Sift
Uncertain
D;.;D;.;D
Sift4G
Benign
T;D;D;D;D
Polyphen
P;.;D;.;.
Vest4
MVP
MPC
0.40
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at