10-48405106-GATATATAT-GATATAT

Variant names:

• chr10-48405106-GAT-G
• rs10657070
• NM_001323329.2:c.252+146_252+147delAT

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+146_252+147delAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0608 in 233,612 control chromosomes in the GnomAD database, including 233 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.048 (179 hom., cov: 0)
  • Exomes 𝑓: 0.081 (54 hom.)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.163
• Publications: 1 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 10-48405106-GAT-G is Benign according to our data. Variant chr10-48405106-GAT-G is described in ClinVar as Benign. ClinVar VariationId is 1272666.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0739 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+146_252+147delAT		intron	N/A	NP_001310258.1	P45983-1
	MAPK8	NM_001278547.2		c.252+146_252+147delAT		intron	N/A	NP_001265476.1	A1L4K2
	MAPK8	NM_001323322.2		c.252+146_252+147delAT		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+126_252+127delAT		intron	N/A	ENSP00000363304.1	P45983-1
	MAPK8	ENST00000374176.8	TSL:1	c.252+126_252+127delAT		intron	N/A	ENSP00000363291.4	P45983-4
	MAPK8	ENST00000374179.8	TSL:1	c.252+126_252+127delAT		intron	N/A	ENSP00000363294.3	P45983-3

Frequencies

GnomAD3 genomes AF: 0.0485 AC: 7005 AN: 144458 Hom.: 180 Cov.: 0

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.0280

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.0184

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0338

Gnomad NFE AF: 0.0409

Gnomad OTH AF: 0.0488

GnomAD4 exome AF: 0.0808 AC: 7198 AN: 89094 Hom.: 54 AF XY: 0.0784 AC XY: 3748 AN XY: 47806

African (AFR) AF: 0.184 AC: 501 AN: 2718

American (AMR) AF: 0.105 AC: 353 AN: 3354

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 290 AN: 2652

East Asian (EAS) AF: 0.0597 AC: 366 AN: 6134

South Asian (SAS) AF: 0.0231 AC: 65 AN: 2818

European-Finnish (FIN) AF: 0.0620 AC: 556 AN: 8966

Middle Eastern (MID) AF: 0.0777 AC: 30 AN: 386

European-Non Finnish (NFE) AF: 0.0802 AC: 4543 AN: 56668

Other (OTH) AF: 0.0915 AC: 494 AN: 5398

GnomAD4 genome AF: 0.0485 AC: 7003 AN: 144518 Hom.: 179 Cov.: 0 AF XY: 0.0469 AC XY: 3292 AN XY: 70210

African (AFR) AF: 0.0761 AC: 3027 AN: 39770

American (AMR) AF: 0.0373 AC: 545 AN: 14618

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 123 AN: 3362

East Asian (EAS) AF: 0.0183 AC: 91 AN: 4986

South Asian (SAS) AF: 0.0169 AC: 76 AN: 4510

European-Finnish (FIN) AF: 0.0386 AC: 330 AN: 8542

Middle Eastern (MID) AF: 0.0292 AC: 8 AN: 274

European-Non Finnish (NFE) AF: 0.0409 AC: 2682 AN: 65600

Other (OTH) AF: 0.0485 AC: 97 AN: 2000

Alfa AF: 0.0406 Hom.: 648

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		0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10657070; hg19: chr10-49613149;