NM_002754.5:c.115G>T

Variant names:

• chr6-36130697-G-T
• NM_002754.5:c.115G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002754.5(MAPK13):​c.115G>T​(p.Val39Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,294,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: MAPK13 NM_002754.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.71

Genes affected

MAPK13 (HGNC:6875): (mitogen-activated protein kinase 13) This gene encodes a member of the mitogen-activated protein (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. The encoded protein is a p38 MAP kinase and is activated by proinflammatory cytokines and cellular stress. Substrates of the encoded protein include the transcription factor ATF2 and the microtubule dynamics regulator stathmin. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.909

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK13	NM_002754.5	c.115G>T	p.Val39Leu	missense_variant	Exon 1 of 12	ENST00000211287.9	NP_002745.1
MAPK13	NR_072996.2	n.185G>T		non_coding_transcript_exon_variant	Exon 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK13	ENST00000211287.9	c.115G>T	p.Val39Leu	missense_variant	Exon 1 of 12	1	NM_002754.5	ENSP00000211287.4

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000154 AC: 2 AN: 1294930 Hom.: 0 Cov.: 26 AF XY: 0.00000308 AC XY: 2 AN XY: 648990

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000203

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Pathogenic	0.65	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Pathogenic	3.2	M;M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.7	D;D
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.17	B;.
Vest4		0.76
MutPred		0.80		Loss of MoRF binding (P = 0.1232);Loss of MoRF binding (P = 0.1232);
MVP		0.82
MPC		0.28
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.96
gMVP		0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-36098474;