19-38217477-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001135155.3(DPF1):​c.710G>A​(p.Arg237Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000132 in 1,513,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R237L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 31)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: DPF1 NM_001135155.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30152625).

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>A	p.Arg237Gln	missense	Exon 7 of 12	NP_001128627.2	Q92782-2
	DPF1	NM_001289978.2		c.710G>A	p.Arg237Gln	missense	Exon 7 of 12	NP_001276907.2	C8C3P2
	DPF1	NM_001363579.1		c.713G>A	p.Arg238Gln	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>A	p.Arg237Gln	missense	Exon 7 of 12	ENSP00000347716.5	Q92782-2
	DPF1	ENST00000614244.4	TSL:1	c.710G>A	p.Arg237Gln	missense	Exon 7 of 12	ENSP00000483226.1	C8C3P2
	DPF1	ENST00000412732.5	TSL:1	c.545G>A	p.Arg182Gln	missense	Exon 7 of 12	ENSP00000412098.1	Q92782-3

Frequencies

GnomAD3 genomes AF: 0.00000667 AC: 1 AN: 150030 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000245

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.34e-7 AC: 1 AN: 1363122 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 672088

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30390

American (AMR) AF: 0.00 AC: 0 AN: 34498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23728

East Asian (EAS) AF: 0.00 AC: 0 AN: 33044

South Asian (SAS) AF: 0.00 AC: 0 AN: 78862

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5342

European-Non Finnish (NFE) AF: 9.47e-7 AC: 1 AN: 1055932

Other (OTH) AF: 0.00 AC: 0 AN: 55496

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000667 AC: 1 AN: 150030 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73102

African (AFR) AF: 0.0000245 AC: 1 AN: 40878

American (AMR) AF: 0.00 AC: 0 AN: 14962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 4930

South Asian (SAS) AF: 0.00 AC: 0 AN: 4662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67602

Other (OTH) AF: 0.00 AC: 0 AN: 2064

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.080
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	0.066	D
PhyloP100		3.2
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.40
Sift	Benign	0.073	T
Sift4G	Benign	0.57	T
Polyphen		0.96	D
Vest4		0.27
MutPred		0.51		Loss of MoRF binding (P = 0.0338)
MVP		0.44
MPC		1.4
ClinPred		0.95	D
GERP RS		3.1
gMVP		0.80
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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;