10-48435183-A-G

Position:

• chr10-48435183-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001323329.2(MAPK8):​c.*154A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0986 in 559,926 control chromosomes in the GnomAD database, including 3,441 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (771 hom., cov: 32)
  • Exomes 𝑓: 0.10 (2670 hom.)
• Consequence: MAPK8 NM_001323329.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.92

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]

ARHGAP22 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 10-48435183-A-G is Benign according to our data. Variant chr10-48435183-A-G is described in ClinVar as [Benign]. Clinvar id is 1276513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK8	NM_001323329.2	c.*154A>G		3_prime_UTR_variant	12/12	ENST00000374189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK8	ENST00000374189.6	c.*154A>G		3_prime_UTR_variant	12/12	5	NM_001323329.2	A1

Frequencies

GnomAD3 genomes AF: 0.0849 AC: 12915 AN: 152098 Hom.: 772 Cov.: 32

Gnomad AFR AF: 0.0231

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0336

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0923

GnomAD4 exome AF: 0.104 AC: 42276 AN: 407710 Hom.: 2670 Cov.: 6 AF XY: 0.102 AC XY: 21337 AN XY: 209738

Gnomad4 AFR exome AF: 0.0212

Gnomad4 AMR exome AF: 0.0585

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.000224

Gnomad4 SAS exome AF: 0.0316

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.0998

GnomAD4 genome AF: 0.0848 AC: 12911 AN: 152216 Hom.: 771 Cov.: 32 AF XY: 0.0847 AC XY: 6300 AN XY: 74414

Gnomad4 AFR AF: 0.0230

Gnomad4 AMR AF: 0.0633

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0334

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.0919

Alfa AF: 0.115 Hom.: 1223

Bravo AF: 0.0776

Asia WGS AF: 0.0150 AC: 51 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	-0.37
CADD	Benign	15
DANN	Benign	0.91

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: rs1062225; hg19: chr10-49643226;