14-72723725-C-T

Position:

• chr14-72723725-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001280542.3(DPF3):​c.433G>A​(p.Val145Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000703 in 1,421,806 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: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: DPF3 NM_001280542.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34279788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPF3	NM_001280542.3	c.433G>A	p.Val145Ile	missense_variant	5/11	ENST00000556509.6
DPF3	NM_001280544.2	c.598G>A	p.Val200Ile	missense_variant	5/10
DPF3	NM_001280543.2	c.463G>A	p.Val155Ile	missense_variant	6/11
DPF3	NM_012074.5	c.433G>A	p.Val145Ile	missense_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPF3	ENST00000556509.6	c.433G>A	p.Val145Ile	missense_variant	5/11	1	NM_001280542.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1421806 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 706870

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000261

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Apr 15, 2022

The c.433G>A (p.V145I) 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 433, causing the valine (V) at amino acid position 145 to be replaced by an isoleucine (I). 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	0.12
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T;T;.;.;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D;D;D;D;.
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.34	T;T;T;T;T
MetaSVM	Uncertain	0.50	D
MutationAssessor	Benign	1.3	L;.;L;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.28	N;.;N;.;N
REVEL	Uncertain	0.30
Sift	Benign	0.47	T;.;T;.;T
Sift4G	Benign	0.39	T;T;T;T;T
Polyphen		0.84	P;.;B;.;.
Vest4		0.58
MutPred		0.28		Gain of helix (P = 0.0082);.;Gain of helix (P = 0.0082);.;.;
MVP		0.59
MPC		0.75
ClinPred		0.85	D
GERP RS		5.1
Varity_R		0.11
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr14-73190433;