10-48405106-GATATATAT-GATATATATAT

Variant names:

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

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+147dupAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 232,544 control chromosomes in the GnomAD database, including 14,932 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (14800 hom., cov: 0)
  • Exomes 𝑓: 0.26 (132 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-G-GAT is Benign according to our data. Variant chr10-48405106-G-GAT is described in ClinVar as Benign. ClinVar VariationId is 1232348.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 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+147dupAT		intron	N/A	NP_001310258.1	P45983-1
	MAPK8	NM_001278547.2		c.252+146_252+147dupAT		intron	N/A	NP_001265476.1	A1L4K2
	MAPK8	NM_001323322.2		c.252+146_252+147dupAT		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+125_252+126insAT		intron	N/A	ENSP00000363304.1	P45983-1
	MAPK8	ENST00000374176.8	TSL:1	c.252+125_252+126insAT		intron	N/A	ENSP00000363291.4	P45983-4
	MAPK8	ENST00000374179.8	TSL:1	c.252+125_252+126insAT		intron	N/A	ENSP00000363294.3	P45983-3

Frequencies

GnomAD3 genomes AF: 0.446 AC: 64344 AN: 144214 Hom.: 14814 Cov.: 0

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.463

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.458

GnomAD4 exome AF: 0.262 AC: 23117 AN: 88270 Hom.: 132 AF XY: 0.266 AC XY: 12595 AN XY: 47370

African (AFR) AF: 0.161 AC: 437 AN: 2716

American (AMR) AF: 0.241 AC: 806 AN: 3350

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 567 AN: 2624

East Asian (EAS) AF: 0.419 AC: 2568 AN: 6124

South Asian (SAS) AF: 0.101 AC: 284 AN: 2816

European-Finnish (FIN) AF: 0.264 AC: 2329 AN: 8828

Middle Eastern (MID) AF: 0.211 AC: 81 AN: 384

European-Non Finnish (NFE) AF: 0.263 AC: 14711 AN: 56034

Other (OTH) AF: 0.247 AC: 1334 AN: 5394

GnomAD4 genome AF: 0.446 AC: 64343 AN: 144274 Hom.: 14800 Cov.: 0 AF XY: 0.451 AC XY: 31596 AN XY: 70100

African (AFR) AF: 0.307 AC: 12203 AN: 39696

American (AMR) AF: 0.429 AC: 6265 AN: 14594

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1296 AN: 3362

East Asian (EAS) AF: 0.828 AC: 4127 AN: 4982

South Asian (SAS) AF: 0.556 AC: 2502 AN: 4496

European-Finnish (FIN) AF: 0.502 AC: 4270 AN: 8502

Middle Eastern (MID) AF: 0.467 AC: 128 AN: 274

European-Non Finnish (NFE) AF: 0.491 AC: 32203 AN: 65522

Other (OTH) AF: 0.457 AC: 911 AN: 1992

Alfa AF: 0.445 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

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

Other links and lift over

dbSNP: rs10657070; hg19: chr10-49613149;