chr19-38218964-C-A

Variant names:

• chr19-38218964-C-A
• rs370726056
• NM_001135155.3:c.393G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001135155.3(DPF1):​c.393G>T​(p.Glu131Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,614,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: DPF1 NM_001135155.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00100
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07422769).
• BS2: High AC in GnomAd4 at 13 AD gene.

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.393G>T	p.Glu131Asp	missense	Exon 4 of 12	NP_001128627.2	Q92782-2
	DPF1	NM_001289978.2		c.393G>T	p.Glu131Asp	missense	Exon 4 of 12	NP_001276907.2	C8C3P2
	DPF1	NM_001363579.1		c.396G>T	p.Glu132Asp	missense	Exon 4 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.393G>T	p.Glu131Asp	missense	Exon 4 of 12	ENSP00000347716.5	Q92782-2
	DPF1	ENST00000614244.4	TSL:1	c.393G>T	p.Glu131Asp	missense	Exon 4 of 12	ENSP00000483226.1	C8C3P2
	DPF1	ENST00000420980.8	TSL:1	c.393G>T	p.Glu131Asp	missense	Exon 4 of 11	ENSP00000397354.3	Q92782-1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152244 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000796 AC: 20 AN: 251354 AF XY: 0.0000663

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000102 AC: 149 AN: 1461866 Hom.: 0 Cov.: 33 AF XY: 0.000102 AC XY: 74 AN XY: 727236

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000122 AC: 136 AN: 1112002

Other (OTH) AF: 0.000132 AC: 8 AN: 60394

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152244 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74388

African (AFR) AF: 0.00 AC: 0 AN: 41470

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000165 Hom.: 0

Bravo AF: 0.0000567

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.000109

EpiControl AF: 0.000119

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	0.067
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.030	N
PhyloP100		0.0010
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.53	N
REVEL	Benign	0.12
Sift	Benign	0.51	T
Sift4G	Benign	0.70	T
Polyphen		0.0	B
Vest4		0.22
MutPred		0.24		Gain of loop (P = 0.0097)
MVP		0.18
MPC		0.85
ClinPred		0.056	T
GERP RS		1.7
Varity_R		0.082
gMVP		0.25
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

dbSNP: rs370726056; hg19: chr19-38709604;