chr14-72671303-C-A

Position:

• chr14-72671303-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001280542.3(DPF3):​c.871+2937G>T variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DPF3 NM_001280542.3 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.99

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23936579).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPF3	NM_001280542.3	c.871+2937G>T		intron_variant		ENST00000556509.6
DPF3	NM_001280544.2	c.1072G>T	p.Ala358Ser	missense_variant	9/10
DPF3	NM_001280543.2	c.937G>T	p.Ala313Ser	missense_variant	10/11
DPF3	NM_012074.5	c.907G>T	p.Ala303Ser	missense_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPF3	ENST00000556509.6	c.871+2937G>T		intron_variant		1	NM_001280542.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

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

Aug 23, 2021

The c.907G>T (p.A303S) alteration is located in exon 9 (coding exon 9) of the DPF3 gene. This alteration results from a G to T substitution at nucleotide position 907, causing the alanine (A) at amino acid position 303 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
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0032	T;.;.;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.60	T;T;T;.
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.89	T
MutationTaster	Benign	1.0	D;D;N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.29	.;N;.;N
REVEL	Benign	0.16
Sift	Benign	0.43	.;T;.;T
Sift4G	Benign	0.49	T;T;T;T
Polyphen		0.86	.;P;.;.
Vest4		0.39
MutPred		0.17		.;Gain of phosphorylation at A303 (P = 0.0093);.;.;
MVP		0.63
MPC		0.36
ClinPred		0.48	T
GERP RS		6.1
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr14-73138011;