11-65598580-G-A

Position:

• chr11-65598580-G-A

Variant summary

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

The NM_002419.4(MAP3K11):​c.2255C>T​(p.Thr752Ile) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAP3K11 NM_002419.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.12

Genes affected

MAP3K11 (HGNC:6850): (mitogen-activated protein kinase kinase kinase 11) The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase contains a SH3 domain and a leucine zipper-basic motif. This kinase preferentially activates MAPK8/JNK kinase, and functions as a positive regulator of JNK signaling pathway. This kinase can directly phosphorylate, and activates IkappaB kinase alpha and beta, and is found to be involved in the transcription activity of NF-kappaB mediated by Rho family GTPases and CDC42. [provided by RefSeq, Jul 2008]

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=0.17693034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K11	NM_002419.4	c.2255C>T	p.Thr752Ile	missense_variant	10/10	ENST00000309100.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K11	ENST00000309100.8	c.2255C>T	p.Thr752Ile	missense_variant	10/10	1	NM_002419.4	P1
MAP3K11	ENST00000530153.5	c.1484C>T	p.Thr495Ile	missense_variant	10/10	2
MAP3K11	ENST00000532507.5	c.503C>T	p.Thr168Ile	missense_variant	5/5	2
MAP3K11	ENST00000524848.5	c.*675-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T;.
Eigen	Benign	0.083
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.34	N;.;.
MutationTaster	Benign	0.97	D;N;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.37	N;N;N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D;D;D
Sift4G	Benign	0.19	T;T;T
Polyphen		0.68	P;.;.
Vest4		0.21
MutPred		0.15		Loss of phosphorylation at T752 (P = 0.0041);.;.;
MVP		0.86
MPC		0.63
ClinPred		0.62	D
GERP RS		5.7
Varity_R		0.16
gMVP		0.19

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: chr11-65366051;