14-72714438-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001280542.3(DPF3):c.589C>T(p.Pro197Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DPF3 NM_001280542.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.05

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.847

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPF3	NM_001280542.3	c.589C>T	p.Pro197Ser	missense_variant	6/11	ENST00000556509.6
DPF3	NM_001280544.2	c.754C>T	p.Pro252Ser	missense_variant	6/10
DPF3	NM_001280543.2	c.619C>T	p.Pro207Ser	missense_variant	7/11
DPF3	NM_012074.5	c.589C>T	p.Pro197Ser	missense_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPF3	ENST00000556509.6	c.589C>T	p.Pro197Ser	missense_variant	6/11	1	NM_001280542.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

The c.589C>T (p.P197S) alteration is located in exon 6 (coding exon 6) of the DPF3 gene. This alteration results from a C to T substitution at nucleotide position 589, causing the proline (P) at amino acid position 197 to be replaced by a serine (S). 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
Cadd	Pathogenic	28
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.32	T;T;.;.;.
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D;D;D;D;.
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.85	D;D;D;D;D
MetaSVM	Pathogenic	0.96	D
MutationAssessor	Uncertain	2.7	M;.;M;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-7.2	D;.;D;.;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0020	D;.;D;.;D
Sift4G	Uncertain	0.012	D;D;D;D;D
Polyphen		0.98	D;.;D;.;.
Vest4		0.72
MutPred		0.38		Loss of catalytic residue at P197 (P = 0.0572);.;Loss of catalytic residue at P197 (P = 0.0572);.;.;
MVP		0.90
MPC		0.56
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.52
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-73181146;