Genetic Variant DBNDD1:p.Arg141Gln (chr16-90006390-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001042610.3(DBNDD1):c.422G>A(p.Arg141Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000585 in 1,607,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

DBNDD1
NM_001042610.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.335

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02517569).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042610.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DBNDD1	NM_001042610.3	MANE Select	c.422G>A	p.Arg141Gln	missense	Exon 4 of 4	NP_001036075.1	Q9H9R9-1
DBNDD1	NM_024043.4		c.482G>A	p.Arg161Gln	missense	Exon 4 of 4	NP_076948.2	Q9H9R9-2
DBNDD1	NM_001288708.2		c.422G>A	p.Arg141Gln	missense	Exon 5 of 5	NP_001275637.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DBNDD1	ENST00000002501.11	TSL:2 MANE Select	c.422G>A	p.Arg141Gln	missense	Exon 4 of 4	ENSP00000002501.6	Q9H9R9-1
DBNDD1	ENST00000304733.8	TSL:1	c.482G>A	p.Arg161Gln	missense	Exon 4 of 4	ENSP00000306407.3	Q9H9R9-2
DBNDD1	ENST00000930202.1		c.464G>A	p.Arg155Gln	missense	Exon 4 of 4	ENSP00000600261.1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000958

AC:

AN:

239982

AF XY:

0.0000917

show subpopulations

Gnomad AFR exome

AF:

0.000463

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000364

Gnomad NFE exome

AF:

0.00000908

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000481

AC:

AN:

1455124

Hom.:

Cov.:

AF XY:

0.0000566

AC XY:

AN XY:

724000

show subpopulations

African (AFR)

AF:

0.000478

AC:

AN:

33478

American (AMR)

AF:

0.000112

AC:

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26096

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39664

South Asian (SAS)

AF:

0.000279

AC:

AN:

85992

European-Finnish (FIN)

AF:

0.000316

AC:

AN:

47494

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111704

Other (OTH)

AF:

0.0000166

AC:

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000158

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.000507

AC:

AN:

41430

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000319

Hom.:

Bravo

AF:

0.000155

ESP6500AA

AF:

0.000991

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.027

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.31

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0074

MetaRNN

Benign

0.025

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

0.34

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.81

REVEL

Benign

0.048

Sift

Benign

0.15

Sift4G

Benign

0.38

Polyphen

0.44

Vest4

0.089

MVP

0.014

MPC

0.16

ClinPred

0.013

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.024

gMVP

0.039

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over