16-90006417-T-C

Variant names:

• chr16-90006417-T-C
• NM_001042610.3:c.395A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001042610.3(DBNDD1):​c.395A>G​(p.Glu132Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E132K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DBNDD1 NM_001042610.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34308505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBNDD1	NM_001042610.3	c.395A>G	p.Glu132Gly	missense_variant	Exon 4 of 4	ENST00000002501.11	NP_001036075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBNDD1	ENST00000002501.11	c.395A>G	p.Glu132Gly	missense_variant	Exon 4 of 4	2	NM_001042610.3	ENSP00000002501.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.455A>G (p.E152G) alteration is located in exon 4 (coding exon 4) of the DBNDD1 gene. This alteration results from a A to G substitution at nucleotide position 455, causing the glutamic acid (E) at amino acid position 152 to be replaced by a glycine (G). 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	0.092
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	.;T;.;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.77	T;T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.2	.;M;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.5	D;D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.29
MutPred		0.38		.;Gain of helix (P = 0.0093);.;.;
MVP		0.27
MPC		0.53
ClinPred		0.95	D
GERP RS		5.4
Varity_R		0.33
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-90072825;