6-36130593-T-G

Position:

• chr6-36130593-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002754.5(MAPK13):​c.11T>G​(p.Ile4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: MAPK13 NM_002754.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.287

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028421402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK13	NM_002754.5	c.11T>G	p.Ile4Ser	missense_variant	1/12	ENST00000211287.9	NP_002745.1
MAPK13	NR_072996.2	n.81T>G		non_coding_transcript_exon_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK13	ENST00000211287.9	c.11T>G	p.Ile4Ser	missense_variant	1/12	1	NM_002754.5	ENSP00000211287	P1
MAPK13	ENST00000373766.9	c.11T>G	p.Ile4Ser	missense_variant	1/10	1		ENSP00000362871
MAPK13	ENST00000476951.5	n.148-26T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2022

The c.11T>G (p.I4S) alteration is located in exon 1 (coding exon 1) of the MAPK13 gene. This alteration results from a T to G substitution at nucleotide position 11, causing the isoleucine (I) at amino acid position 4 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.74
DEOGEN2	Benign	0.083	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.62	T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.028	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.3	N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	1.2	N;N
REVEL	Benign	0.068
Sift	Benign	0.76	T;T
Sift4G	Benign	0.73	T;T
Polyphen		0.0	B;.
Vest4		0.099
MutPred		0.29		Gain of disorder (P = 0.0127);Gain of disorder (P = 0.0127);
MVP		0.34
MPC		0.27
ClinPred		0.042	T
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.40

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: chr6-36098370;