Variant 16-90009419-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001042610.3(DBNDD1):c.43G>A(p.Glu15Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00061 in 1,611,654 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00060 ( 2 hom. )

Consequence

DBNDD1
NM_001042610.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.79

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0068715215).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBNDD1	NM_001042610.3 link	c.43G>A	p.Glu15Lys	missense_variant	2/4	ENST00000002501.11	NP_001036075.1	Q9H9R9-1
DBNDD1	NM_024043.4 link	c.103G>A	p.Glu35Lys	missense_variant	2/4		NP_076948.2	Q9H9R9-2
DBNDD1	NM_001288708.2 link	c.43G>A	p.Glu15Lys	missense_variant	3/5		NP_001275637.1	Q9H9R9
DBNDD1	NM_001288709.2 link	c.-204G>A		5_prime_UTR_variant	2/4		NP_001275638.2	Q9H9R9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBNDD1	ENST00000002501.11 link	c.43G>A	p.Glu15Lys	missense_variant	2/4	2	NM_001042610.3	ENSP00000002501.6		Q9H9R9-1

Frequencies

GnomAD3 genomes

AF:

0.000729

AC:

111

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000955

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000866

AC:

214

AN:

247238

Hom.:

AF XY:

0.000885

AC XY:

119

AN XY:

134414

show subpopulations

Gnomad AFR exome

AF:

0.0000648

Gnomad AMR exome

AF:

0.00177

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000752

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000871

Gnomad OTH exome

AF:

0.00249

GnomAD4 exome

AF:

0.000598

AC:

872

AN:

1459294

Hom.:

Cov.:

AF XY:

0.000623

AC XY:

452

AN XY:

725988

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.00165

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000533

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000569

Gnomad4 OTH exome

AF:

0.000762

GnomAD4 genome

AF:

0.000729

AC:

111

AN:

152360

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000956

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000791

Hom.:

Bravo

AF:

0.000620

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000594

AC:

ExAC

AF:

0.000851

AC:

103

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00130

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

Mar 28, 2022

The c.103G>A (p.E35K) alteration is located in exon 2 (coding exon 2) of the DBNDD1 gene. This alteration results from a G to A substitution at nucleotide position 103, causing the glutamic acid (E) at amino acid position 35 to be replaced by a lysine (K). 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

0.084

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

.;T;.;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.86

D;D;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.0069

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

.;M;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.098

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Benign

0.084

T;D;D;T

Polyphen

0.73

P;P;.;.

Vest4

0.40

MVP

0.014

MPC

0.45

ClinPred

0.039

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.15

gMVP

0.26

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