NM_001042610.3:c.394G>C

Variant names:

• chr16-90006418-C-G
• rs569017076
• NM_001042610.3:c.394G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001042610.3(DBNDD1):​c.394G>C​(p.Glu132Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,452,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. E132K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DBNDD1 NM_001042610.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.14
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31926376).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBNDD1	NM_001042610.3	MANE Select	c.394G>C	p.Glu132Gln	missense	Exon 4 of 4	NP_001036075.1	Q9H9R9-1
	DBNDD1	NM_024043.4		c.454G>C	p.Glu152Gln	missense	Exon 4 of 4	NP_076948.2	Q9H9R9-2
	DBNDD1	NM_001288708.2		c.394G>C	p.Glu132Gln	missense	Exon 5 of 5	NP_001275637.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBNDD1	ENST00000002501.11	TSL:2 MANE Select	c.394G>C	p.Glu132Gln	missense	Exon 4 of 4	ENSP00000002501.6	Q9H9R9-1
	DBNDD1	ENST00000304733.8	TSL:1	c.454G>C	p.Glu152Gln	missense	Exon 4 of 4	ENSP00000306407.3	Q9H9R9-2
	DBNDD1	ENST00000930202.1		c.436G>C	p.Glu146Gln	missense	Exon 4 of 4	ENSP00000600261.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452226 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722824

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111814

Other (OTH) AF: 0.00 AC: 0 AN: 60292

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.1
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.23
MutPred		0.40		Gain of MoRF binding (P = 0.0509)
MVP		0.11
MPC		0.53
ClinPred		0.89	D
GERP RS		5.4
Varity_R		0.22
gMVP		0.14

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

Other links and lift over

dbSNP: rs569017076; hg19: chr16-90072826;