Variant 17-21300595-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_145109.3(MAP2K3):c.216T>C(p.Arg72=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,018,696 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 (★).

Frequency

Genomes: 𝑓 0.29 ( 0 hom., cov: 70)

Exomes 𝑓: 0.10 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAP2K3
NM_145109.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.56

Variant links:

Genes affected

MAP2K3 (HGNC:6843): (mitogen-activated protein kinase kinase 3) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is activated by mitogenic and environmental stress, and participates in the MAP kinase-mediated signaling cascade. It phosphorylates and thus activates MAPK14/p38-MAPK. This kinase can be activated by insulin, and is necessary for the expression of glucose transporter. Expression of RAS oncogene is found to result in the accumulation of the active form of this kinase, which thus leads to the constitutive activation of MAPK14, and confers oncogenic transformation of primary cells. The inhibition of this kinase is involved in the pathogenesis of Yersina pseudotuberculosis. Multiple alternatively spliced transcript variants that encode distinct isoforms have been reported for this gene. [provided by RefSeq, Jul 2008]

MAP2K3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 17-21300595-T-C is Benign according to our data. Variant chr17-21300595-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 768845.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.56 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K3	NM_145109.3 linkuse as main transcript	c.216T>C	p.Arg72=	synonymous_variant	4/12	ENST00000342679.9	NP_659731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K3	ENST00000342679.9 linkuse as main transcript	c.216T>C	p.Arg72=	synonymous_variant	4/12	1	NM_145109.3	ENSP00000345083	P1	P46734-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

40828

AN:

139038

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.267

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.291

GnomAD4 exome

AF:

0.105

AC:

106829

AN:

1018696

Hom.:

Cov.:

AF XY:

0.108

AC XY:

54623

AN XY:

505776

show subpopulations

Gnomad4 AFR exome

AF:

0.238

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.164

Gnomad4 EAS exome

AF:

0.171

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.0959

Gnomad4 NFE exome

AF:

0.0957

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.294

AC:

40868

AN:

139148

Hom.:

Cov.:

AF XY:

0.287

AC XY:

19512

AN XY:

67970

show subpopulations

Gnomad4 AFR

AF:

0.383

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.314

Gnomad4 EAS

AF:

0.295

Gnomad4 SAS

AF:

0.265

Gnomad4 FIN

AF:

0.160

Gnomad4 NFE

AF:

0.270

Gnomad4 OTH

AF:

0.293

Alfa

AF:

0.259

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.9

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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