rs886039234

Positions:

• chr6-90571792-CTCCTCT-C

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1 PM2 PM4 PP3 PP5

The ENST00000369329.8(MAP3K7):​c.130_135del​(p.Arg44_Gly45del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAP3K7 ENST00000369329.8 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.91

Genes affected

MAP3K7 (HGNC:6859): (mitogen-activated protein kinase kinase kinase 7) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase mediates the signaling transduction induced by TGF beta and morphogenetic protein (BMP), and controls a variety of cell functions including transcription regulation and apoptosis. In response to IL-1, this protein forms a kinase complex including TRAF6, MAP3K7P1/TAB1 and MAP3K7P2/TAB2; this complex is required for the activation of nuclear factor kappa B. This kinase can also activate MAPK8/JNK, MAP2K4/MKK4, and thus plays a role in the cell response to environmental stresses. Four alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PM1: In a domain Protein kinase (size 255) in uniprot entity M3K7_HUMAN there are 29 pathogenic changes around while only 6 benign (83%) in ENST00000369329.8
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in ENST00000369329.8.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 6-90571792-CTCCTCT-C is Pathogenic according to our data. Variant chr6-90571792-CTCCTCT-C is described in ClinVar as [Pathogenic]. Clinvar id is 264702.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K7	NM_145331.3	c.130_135del	p.Arg44_Gly45del	inframe_deletion	2/17	ENST00000369329.8	NP_663304.1
MAP3K7	NM_003188.4	c.130_135del	p.Arg44_Gly45del	inframe_deletion	2/16		NP_003179.1
MAP3K7	NM_145332.3	c.130_135del	p.Arg44_Gly45del	inframe_deletion	2/16		NP_663305.1
MAP3K7	NM_145333.3	c.130_135del	p.Arg44_Gly45del	inframe_deletion	2/15		NP_663306.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K7	ENST00000369329.8	c.130_135del	p.Arg44_Gly45del	inframe_deletion	2/17	1	NM_145331.3	ENSP00000358335	P3

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Cardiospondylocarpofacial syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs886039234; hg19: chr6-91281511;