Variant 16-90006369-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001042610.3(DBNDD1):c.443C>T(p.Thr148Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000435 in 1,609,184 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

DBNDD1
NM_001042610.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.48

Variant links:

Genes affected

DBNDD1 (HGNC:28455): (dysbindin domain containing 1) Predicted to be involved in negative regulation of protein kinase activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DBNDD1 links:

DBNDD1 (HGNC:):

DBNDD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24391931).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBNDD1	NM_001042610.3 linkuse as main transcript	c.443C>T	p.Thr148Met	missense_variant	4/4	ENST00000002501.11	NP_001036075.1	Q9H9R9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBNDD1	ENST00000002501.11 linkuse as main transcript	c.443C>T	p.Thr148Met	missense_variant	4/4	2	NM_001042610.3	ENSP00000002501.6		Q9H9R9-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152172

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:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000249

AC:

AN:

240882

Hom.:

AF XY:

0.0000305

AC XY:

AN XY:

131240

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000553

Gnomad NFE exome

AF:

0.0000273

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1457012

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724772

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000201

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

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:

0.0000941

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

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

Aug 08, 2023

The c.503C>T (p.T168M) alteration is located in exon 4 (coding exon 4) of the DBNDD1 gene. This alteration results from a C to T substitution at nucleotide position 503, causing the threonine (T) at amino acid position 168 to be replaced by a methionine (M). 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

0.10

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

.;T;.;.

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.24

T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.2

.;M;.;.

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.8

D;D;D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.012

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.076

MutPred

0.60

.;Loss of phosphorylation at T148 (P = 0.0716);.;.;

MVP

0.20

MPC

0.23

ClinPred

0.88

GERP RS

5.6

Varity_R

0.22

gMVP

0.14

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