Genetic Variant NM_004714.3:c.*9C>G (chr19-39825706-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_004714.3(DYRK1B):c.*9C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,547,078 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0015 ( 4 hom. )

Consequence

DYRK1B
NM_004714.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.539

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BS2

High AC in GnomAd4 at 174 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYRK1B	NM_004714.3 link	c.*9C>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000323039.10	NP_004705.1	Q9Y463-1A0A024R0I0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYRK1B	ENST00000323039 link	c.*9C>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_004714.3	ENSP00000312789.4		Q9Y463-1

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

174

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00176

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.00102

AC:

147

AN:

144142

Hom.:

AF XY:

0.00107

AC XY:

AN XY:

77614

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00118

Gnomad ASJ exome

AF:

0.000606

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000483

Gnomad FIN exome

AF:

0.000320

Gnomad NFE exome

AF:

0.00174

Gnomad OTH exome

AF:

0.000959

GnomAD4 exome

AF:

0.00153

AC:

2136

AN:

1394916

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

1098

AN XY:

688160

show subpopulations

Gnomad4 AFR exome

AF:

0.0000949

Gnomad4 AMR exome

AF:

0.000896

Gnomad4 ASJ exome

AF:

0.000596

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000681

Gnomad4 FIN exome

AF:

0.000351

Gnomad4 NFE exome

AF:

0.00181

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.00114

AC:

174

AN:

152162

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00177

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.000215

Hom.:

Bravo

AF:

0.00111

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 18, 2016

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

DYRK1B-related disorder

Benign:1

Jul 12, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.81

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

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