Genetic Variant DPF1:p.Arg29Leu (chr19-38222652-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001135155.3(DPF1):c.86G>T(p.Arg29Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

DPF1
NM_001135155.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.03

Publications

0 publications found

Variant links:

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]

DPF1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.909

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DPF1	NM_001135155.3	MANE Select	c.86G>T	p.Arg29Leu	missense	Exon 2 of 12	NP_001128627.2	Q92782-2
DPF1	NM_001289978.2		c.86G>T	p.Arg29Leu	missense	Exon 2 of 12	NP_001276907.2	C8C3P2
DPF1	NM_001363579.1		c.89G>T	p.Arg30Leu	missense	Exon 2 of 12	NP_001350508.1	J3KQY6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DPF1	ENST00000355526.10	TSL:1 MANE Select	c.86G>T	p.Arg29Leu	missense	Exon 2 of 12	ENSP00000347716.5	Q92782-2
DPF1	ENST00000614244.4	TSL:1	c.86G>T	p.Arg29Leu	missense	Exon 2 of 12	ENSP00000483226.1	C8C3P2
DPF1	ENST00000420980.8	TSL:1	c.86G>T	p.Arg29Leu	missense	Exon 2 of 11	ENSP00000397354.3	Q92782-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41468

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.93

MetaRNN

Pathogenic

0.91

MetaSVM

Pathogenic

0.97

MutationAssessor

Uncertain

2.9

PhyloP100

6.0

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-6.1

REVEL

Pathogenic

0.88

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.80

MutPred

0.63

Loss of catalytic residue at R30 (P = 0.0429)

MVP

0.89

MPC

2.3

ClinPred

1.0

GERP RS

3.4

Varity_R

0.81

gMVP

0.92

Mutation Taster

=241/59

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over