10-48425836-T-TTCTTGTAAATG

Variant names:

• chr10-48425836-T-TTCTTGTAAATG
• rs367743943
• NM_001323329.2:c.689-52_689-51insTCTTGTAAATG

Variant summary

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

The NM_001323329.2(MAPK8):​c.689-52_689-51insTCTTGTAAATG variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, 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.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.410
• Publications: 0 publications found

Genes affected

MAPK8 (HGNC:6881): (mitogen-activated protein kinase 8) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various cell stimuli, and targets specific transcription factors, and thus mediates immediate-early gene expression in response to cell stimuli. The activation of this kinase by tumor-necrosis factor alpha (TNF-alpha) is found to be required for TNF-alpha induced apoptosis. This kinase is also involved in UV radiation induced apoptosis, which is thought to be related to cytochrom c-mediated cell death pathway. Studies of the mouse counterpart of this gene suggested that this kinase play a key role in T cell proliferation, apoptosis and differentiation. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Apr 2016]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323329.2. 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
	MAPK8	NM_001323329.2	MANE Select	c.689-52_689-51insTCTTGTAAATG		intron	N/A	NP_001310258.1	P45983-1
	MAPK8	NM_001278547.2		c.689-52_689-51insTCTTGTAAATG		intron	N/A	NP_001265476.1	A1L4K2
	MAPK8	NM_001323322.2		c.689-52_689-51insTCTTGTAAATG		intron	N/A	NP_001310251.1	P45983-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK8	ENST00000374189.6	TSL:5 MANE Select	c.689-52_689-51insTCTTGTAAATG		intron	N/A	ENSP00000363304.1	P45983-1
	MAPK8	ENST00000374176.8	TSL:1	c.689-52_689-51insTCTTGTAAATG		intron	N/A	ENSP00000363291.4	P45983-4
	MAPK8	ENST00000374179.8	TSL:1	c.689-52_689-51insTCTTGTAAATG		intron	N/A	ENSP00000363294.3	P45983-3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000117 AC: 1 AN: 853500 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 434136

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

African (AFR) AF: 0.0000483 AC: 1 AN: 20700

American (AMR) AF: 0.00 AC: 0 AN: 26476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35066

South Asian (SAS) AF: 0.00 AC: 0 AN: 48506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4106

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 620486

Other (OTH) AF: 0.00 AC: 0 AN: 38856

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.41

Splicing

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

Other links and lift over

dbSNP: rs367743943; hg19: chr10-49633879;