14-72674356-G-A

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

Scores

5
9
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.13
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]

Genome browser will be placed here

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
DPF3NM_001280542.3 linkuse as main transcriptc.755C>T p.Pro252Leu missense_variant 8/11 ENST00000556509.6
DPF3NM_001280544.2 linkuse as main transcriptc.920C>T p.Pro307Leu missense_variant 8/10
DPF3NM_001280543.2 linkuse as main transcriptc.785C>T p.Pro262Leu missense_variant 9/11
DPF3NM_012074.5 linkuse as main transcriptc.755C>T p.Pro252Leu missense_variant 8/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DPF3ENST00000556509.6 linkuse as main transcriptc.755C>T p.Pro252Leu missense_variant 8/111 NM_001280542.3 P1Q92784-1

Frequencies

GnomAD3 genomes
AF:
0.0000198
AC:
3
AN:
151888
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000484
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000811
AC:
2
AN:
246610
Hom.:
0
AF XY:
0.0000150
AC XY:
2
AN XY:
133662
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:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000959
AC:
14
AN:
1460514
Hom.:
0
Cov.:
30
AF XY:
0.00000964
AC XY:
7
AN XY:
726336
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:
0.0000233
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000900
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000198
AC:
3
AN:
151888
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74158
show subpopulations
Gnomad4 AFR
AF:
0.0000484
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000120
AC:
1
ExAC
AF:
0.0000331
AC:
4

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 GeneticsMar 01, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T;T;.;.;.
Eigen
Uncertain
0.67
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;D;D;D;.
M_CAP
Uncertain
0.092
D
MetaRNN
Benign
0.41
T;T;T;T;T
MetaSVM
Uncertain
0.68
D
MutationAssessor
Uncertain
2.1
M;.;M;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.74
T
PROVEAN
Pathogenic
-5.2
D;.;D;.;D
REVEL
Uncertain
0.59
Sift
Uncertain
0.0050
D;.;D;.;D
Sift4G
Benign
0.084
T;D;D;D;D
Polyphen
0.90
P;.;D;.;.
Vest4
0.43
MVP
0.63
MPC
0.40
ClinPred
0.73
D
GERP RS
5.5
Varity_R
0.26
gMVP
0.28

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs368974268; hg19: chr14-73141064; API