chr10-48405121-A-ATG

Variant names:

• chr10-48405121-A-ATG
• rs67126940
• NM_001323329.2:c.252+141_252+142insGT

Variant summary

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

The NM_001323329.2(MAPK8):​c.252+141_252+142insGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 270,100 control chromosomes in the GnomAD database, including 1,781 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.090 (693 hom., cov: 29)
  • Exomes 𝑓: 0.13 (1088 hom.)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.168
• 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 10-48405121-A-ATG is Benign according to our data. Variant chr10-48405121-A-ATG is described in ClinVar as Benign. ClinVar VariationId is 1273391.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 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.252+141_252+142insGT		intron	N/A	NP_001310258.1	P45983-1
	MAPK8	NM_001278547.2		c.252+141_252+142insGT		intron	N/A	NP_001265476.1	A1L4K2
	MAPK8	NM_001323322.2		c.252+141_252+142insGT		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.252+140_252+141insTG		intron	N/A	ENSP00000363304.1	P45983-1
	MAPK8	ENST00000374176.8	TSL:1	c.252+140_252+141insTG		intron	N/A	ENSP00000363291.4	P45983-4
	MAPK8	ENST00000374179.8	TSL:1	c.252+140_252+141insTG		intron	N/A	ENSP00000363294.3	P45983-3

Frequencies

GnomAD3 genomes AF: 0.0903 AC: 13597 AN: 150528 Hom.: 693 Cov.: 29

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.0679

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0593

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0837

GnomAD4 exome AF: 0.132 AC: 15793 AN: 119474 Hom.: 1088 AF XY: 0.129 AC XY: 8108 AN XY: 62934

African (AFR) AF: 0.0624 AC: 243 AN: 3894

American (AMR) AF: 0.0710 AC: 297 AN: 4184

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 477 AN: 3992

East Asian (EAS) AF: 0.0641 AC: 621 AN: 9694

South Asian (SAS) AF: 0.152 AC: 204 AN: 1346

European-Finnish (FIN) AF: 0.169 AC: 2157 AN: 12760

Middle Eastern (MID) AF: 0.117 AC: 59 AN: 506

European-Non Finnish (NFE) AF: 0.142 AC: 10779 AN: 75696

Other (OTH) AF: 0.129 AC: 956 AN: 7402

GnomAD4 genome AF: 0.0903 AC: 13599 AN: 150626 Hom.: 693 Cov.: 29 AF XY: 0.0912 AC XY: 6708 AN XY: 73564

African (AFR) AF: 0.0511 AC: 2107 AN: 41258

American (AMR) AF: 0.0678 AC: 1028 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3462

East Asian (EAS) AF: 0.0590 AC: 304 AN: 5152

South Asian (SAS) AF: 0.102 AC: 489 AN: 4778

European-Finnish (FIN) AF: 0.142 AC: 1413 AN: 9924

Middle Eastern (MID) AF: 0.0979 AC: 28 AN: 286

European-Non Finnish (NFE) AF: 0.111 AC: 7473 AN: 67596

Other (OTH) AF: 0.0833 AC: 174 AN: 2088

Alfa AF: 0.0367 Hom.: 25

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		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs67126940; hg19: chr10-49613164;