chr6-36130659-T-G

Variant names:

• chr6-36130659-T-G
• rs371857533
• NM_002754.5:c.77T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002754.5(MAPK13):​c.77T>G​(p.Val26Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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: 7.0e-7 (0 hom.)
• Consequence: MAPK13 NM_002754.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.124057144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK13	NM_002754.5	c.77T>G	p.Val26Gly	missense_variant	Exon 1 of 12	ENST00000211287.9	NP_002745.1
MAPK13	NR_072996.2	n.147T>G		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.77T>G	p.Val26Gly	missense_variant	Exon 1 of 12	1	NM_002754.5	ENSP00000211287.4

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428822 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 711198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000289

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	Benign	0.21
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.36	T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.021
Sift	Benign	0.078	T;T
Sift4G	Benign	0.37	T;T
Polyphen		0.0	B;.
Vest4		0.11
MutPred		0.44		Gain of disorder (P = 0.0216);Gain of disorder (P = 0.0216);
MVP		0.22
MPC		0.24
ClinPred		0.056	T
GERP RS		0.080
Varity_R		0.64
gMVP		0.41

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: rs371857533; hg19: chr6-36098436;