NM_003582.4:c.358A>C

Variant names:

• chr1-206647556-A-C
• NM_003582.4:c.358A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003582.4(DYRK3):​c.358A>C​(p.Ser120Arg) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DYRK3 NM_003582.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.60
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15426162).

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.358A>C	p.Ser120Arg	missense	Exon 3 of 3	NP_003573.2	O43781-1
	DYRK3	NM_001004023.3		c.298A>C	p.Ser100Arg	missense	Exon 4 of 4	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.358A>C	p.Ser120Arg	missense	Exon 3 of 3	ENSP00000356076.2	O43781-1
	DYRK3	ENST00000367106.1	TSL:1	c.298A>C	p.Ser100Arg	missense	Exon 4 of 4	ENSP00000356073.1	O43781-2
	DYRK3	ENST00000367108.7	TSL:1	c.298A>C	p.Ser100Arg	missense	Exon 4 of 4	ENSP00000356075.3	O43781-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.15
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.6
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.19
Sift	Benign	0.059	T
Sift4G	Benign	0.16	T
Polyphen		0.059	B
Vest4		0.44
MutPred		0.21		Gain of methylation at K119 (P = 0.0382)
MVP		0.81
MPC		0.37
ClinPred		0.68	D
GERP RS		5.3
Varity_R		0.25
gMVP		0.57
Mutation Taster		=37/63	disease causing

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

Other links and lift over

hg19: chr1-206820901;