chr19-39825857-G-A

Position:

chr19-39825857-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004714.3(DYRK1B):c.1748C>T(p.Ala583Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,605,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

DYRK1B
NM_004714.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 2.63

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03956175).

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYRK1B	NM_004714.3 linkuse as main transcript	c.1748C>T	p.Ala583Val	missense_variant	11/11	ENST00000323039.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYRK1B	ENST00000323039.10 linkuse as main transcript	c.1748C>T	p.Ala583Val	missense_variant	11/11	1	NM_004714.3	P1	Q9Y463-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000611

AC:

AN:

229026

Hom.:

AF XY:

0.0000399

AC XY:

AN XY:

125386

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00126

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000345

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000998

Gnomad OTH exome

AF:

0.000180

GnomAD4 exome

AF:

0.0000413

AC:

AN:

1453430

Hom.:

Cov.:

AF XY:

0.0000401

AC XY:

AN XY:

722478

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000227

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000992

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000159

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000415

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Abdominal obesity-metabolic syndrome 3

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Jan 06, 2023

The c.1748C>T, p.(Ala583Val) missense variant identified in the DYRK1B gene has not been reported in affected individuals in theliterature. The variant is observed in 33 out of ~569,000 heterozygous alleles (no homozygotes) in population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze8), suggesting it is not a common benign variant in the populations represented in those databases. The c.1748C>T variant is located in the last exon of this 11-exongene and is predicted to replace a moderately conserved alanine amino acid with valine at position 583 of the encoded protein. In silico predictions are not in favorof the variant’s damaging effect [REVEL = 0.058]; however, functional studies to support or refute these predictions have not been reported. Due to the lack of compelling evidence for its pathogenicity, the c.1748C>T, p.(Ala583Val) missense variant identified in the DYRK1B gene is reported as a Variant of Uncertain Significance. -

DYRK1B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 27, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.093

T;T;.;.;.

Eigen

Benign

-0.16

Eigen_PC

Benign

0.056

FATHMM_MKL

Uncertain

0.90

M_CAP

Benign

0.015

MetaRNN

Benign

0.040

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.34

N;N;.;.;.

MutationTaster

Benign

0.73

D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.35

.;N;N;.;N

REVEL

Benign

0.058

Sift

Uncertain

0.0070

.;D;D;.;D

Sift4G

Benign

0.25

T;T;T;T;T

Polyphen

0.0080

B;B;B;B;B

Vest4

0.23

MutPred

0.15

Loss of glycosylation at P582 (P = 0.0523);Loss of glycosylation at P582 (P = 0.0523);.;.;.;

MVP

0.54

MPC

0.48

ClinPred

0.10

GERP RS

5.2

Varity_R

0.097

gMVP

0.094

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over