19-38222458-G-A

Variant names:

• chr19-38222458-G-A
• rs1281376548
• NM_001135155.3:c.197C>T

Variant summary

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

The NM_001135155.3(DPF1):​c.197C>T​(p.Ala66Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,431,226 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A66D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: DPF1 NM_001135155.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.38
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.197C>T	p.Ala66Val	missense	Exon 3 of 12	NP_001128627.2	Q92782-2
	DPF1	NM_001289978.2		c.197C>T	p.Ala66Val	missense	Exon 3 of 12	NP_001276907.2	C8C3P2
	DPF1	NM_001363579.1		c.200C>T	p.Ala67Val	missense	Exon 3 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.197C>T	p.Ala66Val	missense	Exon 3 of 12	ENSP00000347716.5	Q92782-2
	DPF1	ENST00000614244.4	TSL:1	c.197C>T	p.Ala66Val	missense	Exon 3 of 12	ENSP00000483226.1	C8C3P2
	DPF1	ENST00000420980.8	TSL:1	c.197C>T	p.Ala66Val	missense	Exon 3 of 11	ENSP00000397354.3	Q92782-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1431226 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 711752

African (AFR) AF: 0.00 AC: 0 AN: 30176

American (AMR) AF: 0.00 AC: 0 AN: 35598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24762

East Asian (EAS) AF: 0.00 AC: 0 AN: 38136

South Asian (SAS) AF: 0.00 AC: 0 AN: 81930

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102788

Other (OTH) AF: 0.00 AC: 0 AN: 58980

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		9.4
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.50
Sift	Benign	0.053	T
Sift4G	Benign	0.22	T
Polyphen		0.93	P
Vest4		0.43
MutPred		0.32		Loss of loop (P = 0.0512)
MVP		0.83
MPC		1.2
ClinPred		0.98	D
GERP RS		3.4
Varity_R		0.36
gMVP		0.57
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1281376548; hg19: chr19-38713098; COSMIC: COSV62792095; COSMIC: COSV62792095;