7-87907210-C-T

Position:

• chr7-87907210-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006716.4(DBF4):​c.1072C>T​(p.Leu358Phe) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DBF4 NM_006716.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.519

Genes affected

DBF4 (HGNC:17364): (DBF4-CDC7 kinase regulatory subunit) Predicted to enable protein serine/threonine kinase activator activity. Predicted to be involved in positive regulation of nuclear cell cycle DNA replication and regulation of cell cycle phase transition. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04211703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBF4	NM_006716.4	c.1072C>T	p.Leu358Phe	missense_variant	12/12	ENST00000265728.6
DBF4	NM_001318061.2	c.400C>T	p.Leu134Phe	missense_variant	12/12
DBF4	NM_001318060.2	c.373C>T	p.Leu125Phe	missense_variant	11/11
DBF4	NM_001318062.2	c.292C>T	p.Leu98Phe	missense_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBF4	ENST00000265728.6	c.1072C>T	p.Leu358Phe	missense_variant	12/12	1	NM_006716.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.1072C>T (p.L358F) alteration is located in exon 12 (coding exon 12) of the DBF4 gene. This alteration results from a C to T substitution at nucleotide position 1072, causing the leucine (L) at amino acid position 358 to be replaced by a phenylalanine (F). 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
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.93
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.60	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.070
Sift	Benign	0.40	T
Sift4G	Benign	0.76	T
Polyphen		0.0010	B
Vest4		0.059
MutPred		0.21		Loss of loop (P = 0.0804);
MVP		0.20
MPC		0.17
ClinPred		0.18	T
GERP RS		1.3
Varity_R		0.031
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1675139590; hg19: chr7-87536525;