NM_004714.3:c.1663C>G

Variant names:

• chr19-39825942-G-C
• rs1555782784
• NM_004714.3:c.1663C>G

Variant summary

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

The NM_004714.3(DYRK1B):​c.1663C>G​(p.Pro555Ala) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DYRK1B NM_004714.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94
• Publications: 0 publications found

Genes affected

DYRK1B (HGNC:3092): (dual specificity tyrosine phosphorylation regulated kinase 1B) This gene encodes a member of a family of nuclear-localized protein kinases. The encoded protein participates in the regulation of the cell cycle. Expression of this gene may be altered in tumor cells, and mutations in this gene were found to cause abdominal obesity-metabolic syndrome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

DYRK1B Gene-Disease associations (from GenCC):

• abdominal obesity-metabolic syndrome 3

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

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=0.13908577).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004714.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK1B	NM_004714.3	MANE Select	c.1663C>G	p.Pro555Ala	missense	Exon 11 of 11	NP_004705.1
	DYRK1B	NM_006484.3		c.1579C>G	p.Pro527Ala	missense	Exon 12 of 12	NP_006475.1
	DYRK1B	NM_006483.3		c.1543C>G	p.Pro515Ala	missense	Exon 11 of 11	NP_006474.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK1B	ENST00000323039.10	TSL:1 MANE Select	c.1663C>G	p.Pro555Ala	missense	Exon 11 of 11	ENSP00000312789.4
	DYRK1B	ENST00000593685.5	TSL:5	c.1843C>G	p.Pro615Ala	missense	Exon 11 of 11	ENSP00000469863.2
	DYRK1B	ENST00000348817.7	TSL:5	c.1579C>G	p.Pro527Ala	missense	Exon 12 of 12	ENSP00000221803.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 17, 2017

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.047
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.053
Sift	Benign	0.19	T
Sift4G	Benign	0.75	T
Polyphen		0.018	B
Vest4		0.29
MutPred		0.13		Loss of glycosylation at P555 (P = 0.0079)
MVP		0.53
MPC		1.3
ClinPred		0.18	T
GERP RS		3.9
Varity_R		0.038
gMVP		0.11
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1555782784; hg19: chr19-40316582;