Genetic Variant DBNDD1:p.Val47Glu (chr16-90009322-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001042610.3(DBNDD1):c.140T>A(p.Val47Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,260 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V47G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DBNDD1
NM_001042610.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.332

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08478734).

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.140T>A	p.Val47Glu	missense	Exon 2 of 4	NP_001036075.1	Q9H9R9-1
DBNDD1	NM_024043.4		c.200T>A	p.Val67Glu	missense	Exon 2 of 4	NP_076948.2	Q9H9R9-2
DBNDD1	NM_001288708.2		c.140T>A	p.Val47Glu	missense	Exon 3 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.140T>A	p.Val47Glu	missense	Exon 2 of 4	ENSP00000002501.6	Q9H9R9-1
DBNDD1	ENST00000304733.8	TSL:1	c.200T>A	p.Val67Glu	missense	Exon 2 of 4	ENSP00000306407.3	Q9H9R9-2
DBNDD1	ENST00000930202.1		c.140T>A	p.Val47Glu	missense	Exon 2 of 4	ENSP00000600261.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248870

AF XY:

0.00000740

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461260

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726952

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52844

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111986

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.047

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.66

M_CAP

Benign

0.015

MetaRNN

Benign

0.085

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.33

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.1

REVEL

Benign

0.13

Sift

Uncertain

0.021

Sift4G

Uncertain

0.022

Polyphen

0.0040

Vest4

0.47

MVP

0.10

MPC

0.29

ClinPred

0.13

GERP RS

2.5

PromoterAI

-0.0072

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.35

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over