chr17-63645770-A-AACAGCATGTC

Variant names:

• chr17-63645770-A-AACAGCATGTC
• rs58194636
• NM_002401.5:c.127-256_127-247dupGTCACAGCAT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002401.5(MAP3K3):​c.127-256_127-247dupGTCACAGCAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 25)
• Consequence: MAP3K3 NM_002401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 1 publications found

Genes affected

MAP3K3 (HGNC:6855): (mitogen-activated protein kinase kinase kinase 3) This gene product is a 626-amino acid polypeptide that is 96.5% identical to mouse Mekk3. Its catalytic domain is closely related to those of several other kinases, including mouse Mekk2, tobacco NPK, and yeast Ste11. Northern blot analysis revealed a 4.6-kb transcript that appears to be ubiquitously expressed. This protein directly regulates the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by activating SEK and MEK1/2 respectively; it does not regulate the p38 pathway. In cotransfection assays, it enhanced transcription from a nuclear factor kappa-B (NFKB)-dependent reporter gene, consistent with a role in the SAPK pathway. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002401.5. 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
	MAP3K3	NM_002401.5	MANE Select	c.127-256_127-247dupGTCACAGCAT		intron	N/A	NP_002392.2
	MAP3K3	NM_203351.3		c.220-256_220-247dupGTCACAGCAT		intron	N/A	NP_976226.1	Q99759-2
	MAP3K3	NM_001363768.2		c.220-256_220-247dupGTCACAGCAT		intron	N/A	NP_001350697.1	J3QRB6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K3	ENST00000361733.8	TSL:1 MANE Select	c.127-264_127-263insACAGCATGTC		intron	N/A	ENSP00000354485.4	Q99759-1
	MAP3K3	ENST00000361357.7	TSL:1	c.220-264_220-263insACAGCATGTC		intron	N/A	ENSP00000354927.3	Q99759-2
	MAP3K3	ENST00000579585.5	TSL:1	c.220-264_220-263insACAGCATGTC		intron	N/A	ENSP00000461988.1	Q99759-2

Frequencies

GnomAD3 genomes Cov.: 25

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

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.15

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

dbSNP: rs58194636; hg19: chr17-61723130;