rs748450780

Variant names:

• chr6-36132648-C-G
• rs748450780
• NM_002754.5:c.277C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-36132648-C-G
• chr6-36132648-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002754.5(MAPK13):​c.277C>G​(p.Pro93Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P93S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAPK13 NM_002754.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125
• Publications: 0 publications found

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]

BRPF3-AS1 (HGNC:55591): (BRPF3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002754.5. 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
	MAPK13	NM_002754.5	MANE Select	c.277C>G	p.Pro93Ala	missense	Exon 3 of 12	NP_002745.1	O15264-1
	MAPK13	NR_072996.2		n.347C>G		non_coding_transcript_exon	Exon 3 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK13	ENST00000211287.9	TSL:1 MANE Select	c.277C>G	p.Pro93Ala	missense	Exon 3 of 12	ENSP00000211287.4	O15264-1
	MAPK13	ENST00000373766.9	TSL:1	c.277C>G	p.Pro93Ala	missense	Exon 3 of 10	ENSP00000362871.5	O15264-2
	MAPK13	ENST00000874020.1		c.277C>G	p.Pro93Ala	missense	Exon 3 of 12	ENSP00000544079.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.49	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.47	N
PhyloP100		-0.13
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Benign	0.13
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.036	D
Polyphen		0.71	P
Vest4		0.38
MutPred		0.64		Loss of phosphorylation at T92 (P = 0.1032)
MVP		0.82
MPC		0.18
ClinPred		0.28	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.31
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs748450780; hg19: chr6-36100425;