1-46562667-CTC-TTT

Variant names:

• chr1-46562667-CTC-TTT
• NM_001135553.4:c.784_786delGAGinsAAA
• MKNK1 p.Glu262Lys

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001135553.4(MKNK1):​c.784_786delGAGinsAAA​(p.Glu262Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MKNK1 NM_001135553.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.83
• Publications: 0 publications found

Genes affected

MKNK1 (HGNC:7110): (MAPK interacting serine/threonine kinase 1) This gene encodes a Ser/Thr protein kinase that interacts with, and is activated by ERK1 and p38 mitogen-activated protein kinases, and thus may play a role in the response to environmental stress and cytokines. This kinase may also regulate transcription by phosphorylating eIF4E via interaction with the C-terminal region of eIF4G. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Jan 2012]

MKNK1-AS1 (HGNC:44129): (MKNK1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135553.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKNK1	NM_001135553.4	MANE Select	c.784_786delGAGinsAAA	p.Glu262Lys	missense	N/A	NP_001129025.2	A0A499FJN1
	MKNK1	NM_003684.7		c.907_909delGAGinsAAA	p.Glu303Lys	missense	N/A	NP_003675.3
	MKNK1	NM_001377337.1		c.802_804delGAGinsAAA	p.Glu268Lys	missense	N/A	NP_001364266.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKNK1	ENST00000371945.10	TSL:1 MANE Select	c.784_786delGAGinsAAA	p.Glu262Lys	missense	N/A	ENSP00000361013.5	A0A499FJN1
	MKNK1	ENST00000371946.9	TSL:1	c.907_909delGAGinsAAA	p.Glu303Lys	missense	N/A	ENSP00000361014.5	A0A499FIS5
	MKNK1	ENST00000342571.7	TSL:1	n.810_812delGAGinsAAA		non_coding_transcript_exon	Exon 8 of 11

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-47028339;