Variant 7-87900307-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006716.4(DBF4):c.767A>T(p.Asp256Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,453,782 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

DBF4
NM_006716.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.00

Variant links:

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]

DBF4 links:

DBF4 (HGNC:):

DBF4 links:

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ACMG classification

Classification made for transcript

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=0.28200454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBF4	NM_006716.4 linkuse as main transcript	c.767A>T	p.Asp256Val	missense_variant	9/12	ENST00000265728.6	NP_006707.1	Q9UBU7-1
DBF4	NM_001318061.2 linkuse as main transcript	c.95A>T	p.Asp32Val	missense_variant	9/12		NP_001304990.1	Q9UBU7B7Z8C6
DBF4	NM_001318060.2 linkuse as main transcript	c.68A>T	p.Asp23Val	missense_variant	8/11		NP_001304989.1	Q9UBU7B4DXK0
DBF4	NM_001318062.2 linkuse as main transcript	c.-14A>T		5_prime_UTR_variant	9/12		NP_001304991.1	Q9UBU7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBF4	ENST00000265728.6 linkuse as main transcript	c.767A>T	p.Asp256Val	missense_variant	9/12	1	NM_006716.4	ENSP00000265728.1		Q9UBU7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000411

AC:

AN:

243228

Hom.:

AF XY:

0.00000758

AC XY:

AN XY:

131922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000900

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1453782

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722914

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.767A>T (p.D256V) alteration is located in exon 9 (coding exon 9) of the DBF4 gene. This alteration results from a A to T substitution at nucleotide position 767, causing the aspartic acid (D) at amino acid position 256 to be replaced by a valine (V). 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

0.21

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.073

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.018

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.7

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.077

Sift

Uncertain

0.012

Sift4G

Uncertain

0.0030

Polyphen

0.31

Vest4

0.40

MutPred

0.26

Gain of methylation at K257 (P = 0.0377);

MVP

0.27

MPC

0.60

ClinPred

0.97

GERP RS

5.5

Varity_R

0.47

gMVP

0.38

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over