chr19-38218625-A-T

Variant names:

• chr19-38218625-A-T
• NM_001135155.3:c.464T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135155.3(DPF1):​c.464T>A​(p.Val155Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 33)
• Consequence: DPF1 NM_001135155.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.813
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15000573).

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.464T>A	p.Val155Glu	missense	Exon 5 of 12	NP_001128627.2	Q92782-2
	DPF1	NM_001289978.2		c.464T>A	p.Val155Glu	missense	Exon 5 of 12	NP_001276907.2	C8C3P2
	DPF1	NM_001363579.1		c.467T>A	p.Val156Glu	missense	Exon 5 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.464T>A	p.Val155Glu	missense	Exon 5 of 12	ENSP00000347716.5	Q92782-2
	DPF1	ENST00000614244.4	TSL:1	c.464T>A	p.Val155Glu	missense	Exon 5 of 12	ENSP00000483226.1	C8C3P2
	DPF1	ENST00000420980.8	TSL:1	c.464T>A	p.Val155Glu	missense	Exon 5 of 11	ENSP00000397354.3	Q92782-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Benign	0.21
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	21
DANN	Benign	0.76
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.67	T
PhyloP100		0.81
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	2.0	N
REVEL	Uncertain	0.40
Sift	Benign	0.43	T
Sift4G	Benign	0.30	T
Polyphen		0.0010	B
Vest4		0.34
MutPred		0.36		Loss of helix (P = 0.0093)
MVP		0.83
MPC		1.5
ClinPred		0.48	T
GERP RS		3.3
Varity_R		0.15
gMVP		0.45
Mutation Taster		=84/16	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

hg19: chr19-38709265;