ENST00000304733.8:c.73G>C

Variant names:

• chr16-90009975-C-G
• rs1319305420
• ENST00000304733.8:c.73G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000304733.8(DBNDD1):​c.73G>C​(p.Gly25Arg) 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. 16/19 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. G25S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DBNDD1 ENST00000304733.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.781
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06788775).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000304733.8. 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.32-545G>C		intron	N/A	NP_001036075.1	Q9H9R9-1
	DBNDD1	NM_024043.4		c.73G>C	p.Gly25Arg	missense	Exon 1 of 4	NP_076948.2	Q9H9R9-2
	DBNDD1	NM_001288708.2		c.32-545G>C		intron	N/A	NP_001275637.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBNDD1	ENST00000304733.8	TSL:1	c.73G>C	p.Gly25Arg	missense	Exon 1 of 4	ENSP00000306407.3	Q9H9R9-2
	DBNDD1	ENST00000002501.11	TSL:2 MANE Select	c.32-545G>C		intron	N/A	ENSP00000002501.6	Q9H9R9-1
	DBNDD1	ENST00000392973.8	TSL:2	c.-496G>C		5_prime_UTR	Exon 1 of 3	ENSP00000376699.3	H3BLZ2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
PhyloP100		-0.78
PromoterAI		-0.038	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1319305420; hg19: chr16-90076383;