17-21290443-G-C

Variant names:

• chr17-21290443-G-C
• rs66859001
• NM_145109.3:c.49+5474G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145109.3(MAP2K3):​c.49+5474G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (0 hom., cov: 47)
  • Failed GnomAD Quality Control
• Consequence: MAP2K3 NM_145109.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K3	NM_145109.3	c.49+5474G>C		intron_variant	Intron 1 of 11	ENST00000342679.9	NP_659731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K3	ENST00000342679.9	c.49+5474G>C		intron_variant	Intron 1 of 11	1	NM_145109.3	ENSP00000345083.4

Frequencies

GnomAD3 genomes AF: 0.488 AC: 63489 AN: 130150 Hom.: 0 Cov.: 47

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.483

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.488 AC: 63531 AN: 130236 Hom.: 0 Cov.: 47 AF XY: 0.488 AC XY: 31048 AN XY: 63686

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.490 AC: 17733 AN: 36226

American (AMR) AF: 0.488 AC: 6412 AN: 13138

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1359 AN: 2814

East Asian (EAS) AF: 0.486 AC: 2153 AN: 4426

South Asian (SAS) AF: 0.467 AC: 1764 AN: 3776

European-Finnish (FIN) AF: 0.490 AC: 4525 AN: 9230

Middle Eastern (MID) AF: 0.469 AC: 107 AN: 228

European-Non Finnish (NFE) AF: 0.488 AC: 28212 AN: 57788

Other (OTH) AF: 0.483 AC: 876 AN: 1812

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.329 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.44
PhyloP100		-0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs66859001; hg19: chr17-21193755;