chr17-45273507-GAG-AAA

Variant names:

• chr17-45273507-GAG-AAA
• NM_003954.5:c.1651_1653delCTCinsTTT
• MAP3K14 p.Leu551Phe

Variant summary

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

The NM_003954.5(MAP3K14):​c.1651_1653delCTCinsTTT​(p.Leu551Phe) variant causes a missense change. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. L551V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAP3K14 NM_003954.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.53
• Publications: 0 publications found

Genes affected

MAP3K14 (HGNC:6853): (mitogen-activated protein kinase kinase kinase 14) This gene encodes mitogen-activated protein kinase kinase kinase 14, which is a serine/threonine protein-kinase. This kinase binds to TRAF2 and stimulates NF-kappaB activity. It shares sequence similarity with several other MAPKK kinases. It participates in an NF-kappaB-inducing signalling cascade common to receptors of the tumour-necrosis/nerve-growth factor (TNF/NGF) family and to the interleukin-1 type-I receptor. [provided by RefSeq, Jul 2008]

MAP3K14 Gene-Disease associations (from GenCC):

• NIK deficiency

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003954.5. 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
	MAP3K14	NM_003954.5	MANE Select	c.1651_1653delCTCinsTTT	p.Leu551Phe	missense	N/A	NP_003945.2	Q99558

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K14	ENST00000344686.8	TSL:1 MANE Select	c.1651_1653delCTCinsTTT	p.Leu551Phe	missense	N/A	ENSP00000478552.1	Q99558
	MAP3K14	ENST00000376926.8	TSL:1	c.1651_1653delCTCinsTTT	p.Leu551Phe	missense	N/A	ENSP00000482657.1	Q99558
	MAP3K14	ENST00000970424.1		c.1669_1671delCTCinsTTT	p.Leu557Phe	missense	N/A	ENSP00000640483.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5

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: chr17-43350874;