NM_001323329.2:c.689-52_689-51insTGTAAATG

Variant names:

• chr10-48425836-T-TTGTAAATG
• rs367743943
• NM_001323329.2:c.689-52_689-51insTGTAAATG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001323329.2(MAPK8):​c.689-52_689-51insTGTAAATG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (19839 hom., cov: 0)
  • Exomes 𝑓: 0.52 (119833 hom.)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 10-48425836-T-TTGTAAATG is Benign according to our data. Variant chr10-48425836-T-TTGTAAATG is described in ClinVar as Benign. ClinVar VariationId is 1177799.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

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_689-51insTGTAAATG		intron	N/A	NP_001310258.1	P45983-1
	MAPK8	NM_001278547.2		c.689-52_689-51insTGTAAATG		intron	N/A	NP_001265476.1	A1L4K2
	MAPK8	NM_001323322.2		c.689-52_689-51insTGTAAATG		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_689-51insTGTAAATG		intron	N/A	ENSP00000363304.1	P45983-1
	MAPK8	ENST00000374176.8	TSL:1	c.689-52_689-51insTGTAAATG		intron	N/A	ENSP00000363291.4	P45983-4
	MAPK8	ENST00000374179.8	TSL:1	c.689-52_689-51insTGTAAATG		intron	N/A	ENSP00000363294.3	P45983-3

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76379 AN: 151684 Hom.: 19839 Cov.: 0

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.539

GnomAD4 exome AF: 0.525 AC: 445782 AN: 849350 Hom.: 119833 Cov.: 12 AF XY: 0.523 AC XY: 225760 AN XY: 431970

African (AFR) AF: 0.344 AC: 7082 AN: 20604

American (AMR) AF: 0.488 AC: 12869 AN: 26346

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 9620 AN: 17124

East Asian (EAS) AF: 0.649 AC: 22720 AN: 34998

South Asian (SAS) AF: 0.358 AC: 17236 AN: 48136

European-Finnish (FIN) AF: 0.521 AC: 21842 AN: 41940

Middle Eastern (MID) AF: 0.604 AC: 2476 AN: 4098

European-Non Finnish (NFE) AF: 0.537 AC: 331398 AN: 617402

Other (OTH) AF: 0.531 AC: 20539 AN: 38702

GnomAD4 genome AF: 0.503 AC: 76404 AN: 151802 Hom.: 19839 Cov.: 0 AF XY: 0.503 AC XY: 37295 AN XY: 74166

African (AFR) AF: 0.373 AC: 15477 AN: 41446

American (AMR) AF: 0.488 AC: 7447 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2033 AN: 3464

East Asian (EAS) AF: 0.638 AC: 3298 AN: 5170

South Asian (SAS) AF: 0.397 AC: 1911 AN: 4814

European-Finnish (FIN) AF: 0.553 AC: 5821 AN: 10532

Middle Eastern (MID) AF: 0.719 AC: 210 AN: 292

European-Non Finnish (NFE) AF: 0.569 AC: 38576 AN: 67802

Other (OTH) AF: 0.533 AC: 1122 AN: 2106

Alfa AF: 0.153 Hom.: 573

Asia WGS AF: 0.484 AC: 1683 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

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: rs367743943; hg19: chr10-49633879;