16-90009383-C-T

Position:

• chr16-90009383-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042610.3(DBNDD1):​c.79G>A​(p.Ala27Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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: 1.09

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.086713225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBNDD1	NM_001042610.3	c.79G>A	p.Ala27Thr	missense_variant	2/4	ENST00000002501.11	NP_001036075.1
DBNDD1	NM_024043.4	c.139G>A	p.Ala47Thr	missense_variant	2/4		NP_076948.2
DBNDD1	NM_001288708.2	c.79G>A	p.Ala27Thr	missense_variant	3/5		NP_001275637.1
DBNDD1	NM_001288709.2	c.-168G>A		5_prime_UTR_variant	2/4		NP_001275638.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBNDD1	ENST00000002501.11	c.79G>A	p.Ala27Thr	missense_variant	2/4	2	NM_001042610.3	ENSP00000002501.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.139G>A (p.A47T) 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 139, causing the alanine (A) at amino acid position 47 to be replaced by a threonine (T). 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	0.070
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	.;T;.;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.75	T;T;T;T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.087	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;L;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.014	D;D;D;D
Sift4G	Benign	0.19	T;T;T;D
Polyphen		0.19	B;B;.;.
Vest4		0.076
MutPred		0.50		.;Gain of glycosylation at A27 (P = 0.0103);.;.;
MVP		0.055
MPC		0.13
ClinPred		0.54	D
GERP RS		4.8
Varity_R		0.083
gMVP		0.13

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: chr16-90075791;