Variant 7-87907454-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006716.4(DBF4):c.1316C>T(p.Thr439Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

DBF4
NM_006716.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.496

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.04614675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBF4	NM_006716.4 linkuse as main transcript	c.1316C>T	p.Thr439Ile	missense_variant	12/12	ENST00000265728.6	NP_006707.1	Q9UBU7-1
DBF4	NM_001318061.2 linkuse as main transcript	c.644C>T	p.Thr215Ile	missense_variant	12/12		NP_001304990.1	Q9UBU7B7Z8C6
DBF4	NM_001318060.2 linkuse as main transcript	c.617C>T	p.Thr206Ile	missense_variant	11/11		NP_001304989.1	Q9UBU7B4DXK0
DBF4	NM_001318062.2 linkuse as main transcript	c.536C>T	p.Thr179Ile	missense_variant	12/12		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.1316C>T	p.Thr439Ile	missense_variant	12/12	1	NM_006716.4	ENSP00000265728.1		Q9UBU7-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250854

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135696

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1461714

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727148

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:

0.0000315

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

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

May 31, 2023

The c.1316C>T (p.T439I) 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 1316, causing the threonine (T) at amino acid position 439 to be replaced by an isoleucine (I). 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

0.090

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

4.4

DANN

Benign

0.83

DEOGEN2

Benign

0.015

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.73

M_CAP

Benign

0.0050

MetaRNN

Benign

0.046

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.60

REVEL

Benign

0.070

Sift

Benign

0.56

Sift4G

Benign

0.53

Polyphen

0.049

Vest4

0.038

MutPred

0.17

Loss of helix (P = 0.0626);

MVP

0.12

MPC

0.16

ClinPred

0.046

GERP RS

3.8

Varity_R

0.044

gMVP

0.062

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

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