19-38217477-C-A

Position:

• chr19-38217477-C-A

Variant summary

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

The NM_001135155.3(DPF1):​c.710G>T​(p.Arg237Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DPF1 NM_001135155.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.23

Genes affected

DPF1 (HGNC:20225): (double PHD fingers 1) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated; nervous system development; and positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm. Predicted to be part of nBAF complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPF1	NM_001135155.3	c.710G>T	p.Arg237Leu	missense_variant	7/12	ENST00000355526.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPF1	ENST00000355526.10	c.710G>T	p.Arg237Leu	missense_variant	7/12	1	NM_001135155.3	P4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 40

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

Dec 20, 2021

The c.791G>T (p.R264L) alteration is located in exon 7 (coding exon 7) of the DPF1 gene. This alteration results from a G to T substitution at nucleotide position 791, causing the arginine (R) at amino acid position 264 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
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T;.;T;.;.;T;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.097
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.96	D;D;D;.;D;D;D
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.23	D
MutationTaster	Benign	0.99	D;D;D;D;D;D
PrimateAI	Uncertain	0.71	T
Sift4G	Benign	0.26	T;T;T;T;T;T;.
Polyphen		0.92	P;.;D;.;P;.;.
Vest4		0.44
MutPred		0.50		.;.;Loss of methylation at K243 (P = 0.0339);.;.;Loss of methylation at K243 (P = 0.0339);.;
MVP		0.66
MPC		2.2
ClinPred		0.88	D
GERP RS		3.1
gMVP		0.88

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: chr19-38708117;