19-38217477-C-A

Variant names:

• chr19-38217477-C-A
• rs2062874207
• NM_001135155.3:c.710G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135155.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPF1	NM_001135155.3	MANE Select	c.710G>T	p.Arg237Leu	missense	Exon 7 of 12	NP_001128627.2	Q92782-2
	DPF1	NM_001289978.2		c.710G>T	p.Arg237Leu	missense	Exon 7 of 12	NP_001276907.2	C8C3P2
	DPF1	NM_001363579.1		c.713G>T	p.Arg238Leu	missense	Exon 7 of 12	NP_001350508.1	J3KQY6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPF1	ENST00000355526.10	TSL:1 MANE Select	c.710G>T	p.Arg237Leu	missense	Exon 7 of 12	ENSP00000347716.5	Q92782-2
	DPF1	ENST00000614244.4	TSL:1	c.710G>T	p.Arg237Leu	missense	Exon 7 of 12	ENSP00000483226.1	C8C3P2
	DPF1	ENST00000412732.5	TSL:1	c.545G>T	p.Arg182Leu	missense	Exon 7 of 12	ENSP00000412098.1	Q92782-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.097
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	0.23	D
PhyloP100		3.2
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.022	D
Sift4G	Benign	0.26	T
Polyphen		0.92	P
Vest4		0.44
MutPred		0.50		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
Mutation Taster		=53/47	polymorphism

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

Other links and lift over

dbSNP: rs2062874207; hg19: chr19-38708117;