19-38217498-C-T

Variant names:

• chr19-38217498-C-T
• rs1347418240
• NM_001135155.3:c.689G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001135155.3(DPF1):​c.689G>A​(p.Arg230His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,395,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DPF1 NM_001135155.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.68

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31983754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPF1	NM_001135155.3	c.689G>A	p.Arg230His	missense_variant	Exon 7 of 12	ENST00000355526.10	NP_001128627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPF1	ENST00000355526.10	c.689G>A	p.Arg230His	missense_variant	Exon 7 of 12	1	NM_001135155.3	ENSP00000347716.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1395360 Hom.: 0 Cov.: 40 AF XY: 0.00000145 AC XY: 1 AN XY: 688140

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.29e-7

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.770G>A (p.R257H) alteration is located in exon 7 (coding exon 7) of the DPF1 gene. This alteration results from a G to A substitution at nucleotide position 770, causing the arginine (R) at amino acid position 257 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.023	T;.;T;.;.;T;T
Eigen	Benign	0.18
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.95	D;D;D;.;D;D;D
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.32	T;T;T;T;T;T;T
MetaSVM	Uncertain	0.43	D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.6	.;N;N;N;N;N;N
REVEL	Uncertain	0.36
Sift	Benign	0.12	.;T;T;T;T;T;T
Sift4G	Benign	0.15	T;T;T;T;T;T;.
Polyphen		0.99	D;.;D;.;D;.;.
Vest4		0.18
MutPred		0.34		.;.;Loss of MoRF binding (P = 0.0685);.;.;Loss of MoRF binding (P = 0.0685);.;
MVP		0.58
MPC		1.7
ClinPred		0.90	D
GERP RS		2.9
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs1347418240; hg19: chr19-38708138;