6-36110403-C-T

Position:

• chr6-36110403-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_139012.3(MAPK14):​c.*1956C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,714 control chromosomes in the GnomAD database, including 1,671 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1667 hom., cov: 33)
  • Exomes 𝑓: 0.15 (4 hom.)
• Consequence: MAPK14 NM_139012.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

Genes affected

MAPK14 (HGNC:6876): (mitogen-activated protein kinase 14) 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 environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase. The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response. Four alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK14	NM_139012.3	c.*1956C>T		3_prime_UTR_variant	12/12	ENST00000229794.9	NP_620581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK14	ENST00000229794.9	c.*1956C>T		3_prime_UTR_variant	12/12	1	NM_139012.3	ENSP00000229794.4
MAPK14	ENST00000229795.8	c.*1956C>T		3_prime_UTR_variant	12/12	1		ENSP00000229795.3

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16252 AN: 152160 Hom.: 1658 Cov.: 33

Gnomad AFR AF: 0.0338

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.0770

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.0902

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0913

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.147 AC: 64 AN: 436 Hom.: 4 Cov.: 0 AF XY: 0.149 AC XY: 39 AN XY: 262

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.107 AC: 16272 AN: 152278 Hom.: 1667 Cov.: 33 AF XY: 0.112 AC XY: 8360 AN XY: 74458

Gnomad4 AFR AF: 0.0337

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.0770

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.0896

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.0913

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0923 Hom.: 238

Bravo AF: 0.116

Asia WGS AF: 0.263 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	15
DANN	Benign	0.90

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: rs8510; hg19: chr6-36078180; COSMIC: COSV57695622; COSMIC: COSV57695622;