1-206648018-ATG-GTA

Variant names:

• chr1-206648018-ATG-GTA
• NM_003582.4:c.820_822delATGinsGTA
• DYRK3 p.Met274Val

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_003582.4(DYRK3):​c.820_822delATGinsGTA​(p.Met274Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. M274L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DYRK3 NM_003582.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.99
• Publications: 0 publications found

Genes affected

DYRK3 (HGNC:3094): (dual specificity tyrosine phosphorylation regulated kinase 3) This gene product belongs to the DYRK family of dual-specificity protein kinases that catalyze autophosphorylation on serine/threonine and tyrosine residues. The members of this family share structural similarity, however, differ in their substrate specificity, suggesting their involvement in different cellular functions. The encoded protein has been shown to autophosphorylate on tyrosine residue and catalyze phosphorylation of histones H3 and H2B in vitro. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

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

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003582.4. 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
	DYRK3	NM_003582.4	MANE Select	c.820_822delATGinsGTA	p.Met274Val	missense	N/A	NP_003573.2	O43781-1
	DYRK3	NM_001004023.3		c.760_762delATGinsGTA	p.Met254Val	missense	N/A	NP_001004023.1	O43781-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK3	ENST00000367109.8	TSL:1 MANE Select	c.820_822delATGinsGTA	p.Met274Val	missense	N/A	ENSP00000356076.2	O43781-1
	DYRK3	ENST00000367106.1	TSL:1	c.760_762delATGinsGTA	p.Met254Val	missense	N/A	ENSP00000356073.1	O43781-2
	DYRK3	ENST00000367108.7	TSL:1	c.760_762delATGinsGTA	p.Met254Val	missense	N/A	ENSP00000356075.3	O43781-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0

Splicing

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

hg19: chr1-206821363;