11-65598412-T-G

Variant names:

• chr11-65598412-T-G
• NM_002419.4:c.2423A>C

Variant summary

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

The NM_002419.4(MAP3K11):​c.2423A>C​(p.Asp808Ala) 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.83

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=0.16257724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K11	NM_002419.4	c.2423A>C	p.Asp808Ala	missense_variant	Exon 10 of 10	ENST00000309100.8	NP_002410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K11	ENST00000309100.8	c.2423A>C	p.Asp808Ala	missense_variant	Exon 10 of 10	1	NM_002419.4	ENSP00000309597.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2423A>C (p.D808A) alteration is located in exon 10 (coding exon 10) of the MAP3K11 gene. This alteration results from a A to C substitution at nucleotide position 2423, causing the aspartic acid (D) at amino acid position 808 to be replaced by an alanine (A). 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	0.13
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T;T;.
Eigen	Benign	-0.082
Eigen_PC	Benign	0.039
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.69	N;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D;D;D
Sift4G	Benign	0.69	T;T;T
Polyphen		0.63	P;.;.
Vest4		0.14
MutPred		0.16		Loss of solvent accessibility (P = 0.0052);.;.;
MVP		0.89
MPC		0.68
ClinPred		0.64	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.33

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: chr11-65365883;