17-21302148-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_145109.3(MAP2K3):c.405C>T(p.Asp135=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (0 hom., cov: 65)
  • Exomes 𝑓: 0.50 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAP2K3 NM_145109.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.35

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 17-21302148-C-T is Benign according to our data. Variant chr17-21302148-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 768849.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.35 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2K3	NM_145109.3	c.405C>T	p.Asp135=	synonymous_variant	6/12	ENST00000342679.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2K3	ENST00000342679.9	c.405C>T	p.Asp135=	synonymous_variant	6/12	1	NM_145109.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 75804 AN: 151726 Hom.: 0 Cov.: 65 FAILED QC

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.500

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.500 AC: 728075 AN: 1456702 Hom.: 1 Cov.: 54 AF XY: 0.500 AC XY: 362335 AN XY: 724920

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.495

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.500 AC: 75861 AN: 151842 Hom.: 0 Cov.: 65 AF XY: 0.500 AC XY: 37105 AN XY: 74264

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.500

Alfa AF: 0.500 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	0.73
Dann	Benign	0.28
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

Other links and lift over

dbSNP: rs62057721; hg19: chr17-21205460; COSMIC: COSV57562638; COSMIC: COSV57562638;