Genetic Variant NM_001042610.3:c.412G>A (chr16-90006400-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001042610.3(DBNDD1):c.412G>A(p.Asp138Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000038 in 1,606,330 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 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

DBNDD1
NM_001042610.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.10

Publications

1 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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18868318).

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.412G>A	p.Asp138Asn	missense	Exon 4 of 4	NP_001036075.1	Q9H9R9-1
DBNDD1	NM_024043.4		c.472G>A	p.Asp158Asn	missense	Exon 4 of 4	NP_076948.2	Q9H9R9-2
DBNDD1	NM_001288708.2		c.412G>A	p.Asp138Asn	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.412G>A	p.Asp138Asn	missense	Exon 4 of 4	ENSP00000002501.6	Q9H9R9-1
DBNDD1	ENST00000304733.8	TSL:1	c.472G>A	p.Asp158Asn	missense	Exon 4 of 4	ENSP00000306407.3	Q9H9R9-2
DBNDD1	ENST00000930202.1		c.454G>A	p.Asp152Asn	missense	Exon 4 of 4	ENSP00000600261.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000334

AC:

AN:

239690

AF XY:

0.0000306

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000168

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.0000399

AC:

AN:

1454270

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

723718

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.000630

AC:

AN:

39678

South Asian (SAS)

AF:

0.0000465

AC:

AN:

86076

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46430

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000216

AC:

AN:

1111782

Other (OTH)

AF:

0.0000829

AC:

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.0000197

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41392

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

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:

0.0000712

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000331

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

0.087

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Benign

-0.061

Eigen_PC

Benign

-0.096

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.78

M_CAP

Benign

0.014

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.2

PhyloP100

4.1

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.26

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.80

Vest4

0.16

MutPred

0.61

Loss of methylation at K133 (P = 0.1377)

MVP

0.076

MPC

0.15

ClinPred

0.20

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.46

gMVP

0.24

Mutation Taster

=86/14

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