10-48410309-T-G

Position:

• chr10-48410309-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001323329.2(MAPK8):​c.450+141T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 602,918 control chromosomes in the GnomAD database, including 3,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.095 (727 hom., cov: 32)
  • Exomes 𝑓: 0.11 (2645 hom.)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.114

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-48410309-T-G is Benign according to our data. Variant chr10-48410309-T-G is described in ClinVar as [Benign]. Clinvar id is 1175647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK8	NM_001323329.2	c.450+141T>G		intron_variant		ENST00000374189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK8	ENST00000374189.6	c.450+141T>G		intron_variant		5	NM_001323329.2	A1

Frequencies

GnomAD3 genomes AF: 0.0953 AC: 14502 AN: 152148 Hom.: 727 Cov.: 32

Gnomad AFR AF: 0.0725

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.0708

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0593

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0867

GnomAD4 exome AF: 0.108 AC: 48508 AN: 450652 Hom.: 2645 Cov.: 7 AF XY: 0.107 AC XY: 24402 AN XY: 227498

Gnomad4 AFR exome AF: 0.0714

Gnomad4 AMR exome AF: 0.0547

Gnomad4 ASJ exome AF: 0.0918

Gnomad4 EAS exome AF: 0.0483

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.0953 AC: 14507 AN: 152266 Hom.: 727 Cov.: 32 AF XY: 0.0964 AC XY: 7174 AN XY: 74452

Gnomad4 AFR AF: 0.0725

Gnomad4 AMR AF: 0.0707

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0591

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0863

Alfa AF: 0.103 Hom.: 104

Bravo AF: 0.0900

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.45
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs56361423; hg19: chr10-49618352; COSMIC: COSV64410647; COSMIC: COSV64410647;