NM_004714.3:c.1839G>T

Variant names:

• chr19-39825766-C-A
• rs772198180
• NM_004714.3:c.1839G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_004714.3(DYRK1B):​c.1839G>T​(p.Gly613Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000764 in 1,570,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000076 (0 hom.)
• Consequence: DYRK1B NM_004714.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.695
• Publications: 1 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), Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 19-39825766-C-A is Benign according to our data. Variant chr19-39825766-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3039127.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.695 with no splicing effect.
• BS2: High AC in GnomAd4 at 12 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK1B	NM_004714.3	MANE Select	c.1839G>T	p.Gly613Gly	synonymous	Exon 11 of 11	NP_004705.1	Q9Y463-1
	DYRK1B	NM_006484.3		c.1755G>T	p.Gly585Gly	synonymous	Exon 12 of 12	NP_006475.1	Q9Y463-3
	DYRK1B	NM_006483.3		c.1719G>T	p.Gly573Gly	synonymous	Exon 11 of 11	NP_006474.1	Q9Y463-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK1B	ENST00000323039.10	TSL:1 MANE Select	c.1839G>T	p.Gly613Gly	synonymous	Exon 11 of 11	ENSP00000312789.4	Q9Y463-1
	DYRK1B	ENST00000593685.5	TSL:5	c.2019G>T	p.Gly673Gly	synonymous	Exon 11 of 11	ENSP00000469863.2	A0A9H4CVU7
	DYRK1B	ENST00000348817.7	TSL:5	c.1755G>T	p.Gly585Gly	synonymous	Exon 12 of 12	ENSP00000221803.4	Q9Y463-3

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152048 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000116 AC: 2 AN: 173050 AF XY: 0.0000106

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000285

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000761 AC: 108 AN: 1418828 Hom.: 0 Cov.: 33 AF XY: 0.0000669 AC XY: 47 AN XY: 702168

African (AFR) AF: 0.0000309 AC: 1 AN: 32380

American (AMR) AF: 0.00 AC: 0 AN: 37266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25428

East Asian (EAS) AF: 0.00 AC: 0 AN: 36958

South Asian (SAS) AF: 0.00 AC: 0 AN: 81830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49908

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5182

European-Non Finnish (NFE) AF: 0.0000926 AC: 101 AN: 1091062

Other (OTH) AF: 0.000102 AC: 6 AN: 58814

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152048 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74252

African (AFR) AF: 0.0000967 AC: 4 AN: 41370

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000567 Hom.: 0

Bravo AF: 0.0000604

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DYRK1B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.5
DANN	Benign	0.63
PhyloP100		0.69

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: rs772198180; hg19: chr19-40316406;