chr11-65598526-G-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4BS2
The NM_002419.4(MAP3K11):c.2309C>T(p.Ser770Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,612,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
MAP3K11
NM_002419.4 missense
NM_002419.4 missense
Scores
1
11
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.63
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity M3K11_HUMAN
BP4
Computational evidence support a benign effect (MetaRNN=0.2812335).
BS2
High AC in GnomAdExome4 at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAP3K11 | NM_002419.4 | c.2309C>T | p.Ser770Leu | missense_variant | 10/10 | ENST00000309100.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAP3K11 | ENST00000309100.8 | c.2309C>T | p.Ser770Leu | missense_variant | 10/10 | 1 | NM_002419.4 | P1 | |
MAP3K11 | ENST00000530153.5 | c.1538C>T | p.Ser513Leu | missense_variant | 10/10 | 2 | |||
MAP3K11 | ENST00000532507.5 | c.557C>T | p.Ser186Leu | missense_variant | 5/5 | 2 | |||
MAP3K11 | ENST00000524848.5 | c.*723C>T | 3_prime_UTR_variant, NMD_transcript_variant | 9/9 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000163 AC: 4AN: 245514Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133422
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GnomAD4 exome AF: 0.00000822 AC: 12AN: 1460696Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 726604
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74378
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Pathogenic
D;D;D
Sift4G
Uncertain
T;D;T
Polyphen
D;.;.
Vest4
MutPred
Loss of phosphorylation at S770 (P = 0.0011);.;.;
MVP
MPC
ClinPred
D
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at