19-38222652-C-T

Variant names:

• chr19-38222652-C-T
• rs1376992383
• NM_001135155.3:c.86G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001135155.3(DPF1):​c.86G>A​(p.Arg29His) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R29L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DPF1 NM_001135155.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.03
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.859

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.86G>A	p.Arg29His	missense	Exon 2 of 12	NP_001128627.2	Q92782-2
	DPF1	NM_001289978.2		c.86G>A	p.Arg29His	missense	Exon 2 of 12	NP_001276907.2	C8C3P2
	DPF1	NM_001363579.1		c.89G>A	p.Arg30His	missense	Exon 2 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.86G>A	p.Arg29His	missense	Exon 2 of 12	ENSP00000347716.5	Q92782-2
	DPF1	ENST00000614244.4	TSL:1	c.86G>A	p.Arg29His	missense	Exon 2 of 12	ENSP00000483226.1	C8C3P2
	DPF1	ENST00000420980.8	TSL:1	c.86G>A	p.Arg29His	missense	Exon 2 of 11	ENSP00000397354.3	Q92782-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456324 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724130

African (AFR) AF: 0.00 AC: 0 AN: 33130

American (AMR) AF: 0.00 AC: 0 AN: 44264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25976

East Asian (EAS) AF: 0.00 AC: 0 AN: 39438

South Asian (SAS) AF: 0.00 AC: 0 AN: 85384

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5154

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109940

Other (OTH) AF: 0.0000166 AC: 1 AN: 60062

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.50	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.87	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		6.0
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-4.2	D
REVEL	Pathogenic	0.86
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.74
MutPred		0.60		Loss of loop (P = 0.0374)
MVP		0.91
MPC		2.3
ClinPred		1.0	D
GERP RS		3.4
Varity_R		0.68
gMVP		0.85
Mutation Taster		=241/59	polymorphism

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

Other links and lift over

dbSNP: rs1376992383; hg19: chr19-38713292;