chr11-65605799-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4BS2

The NM_002419.4(MAP3K11):​c.1793C>T​(p.Ser598Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,562 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: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

MAP3K11
NM_002419.4 missense

Scores

11
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31376535).
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAP3K11NM_002419.4 linkuse as main transcriptc.1793C>T p.Ser598Phe missense_variant 8/10 ENST00000309100.8
MAP3K11XM_047426962.1 linkuse as main transcriptc.1793C>T p.Ser598Phe missense_variant 8/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAP3K11ENST00000309100.8 linkuse as main transcriptc.1793C>T p.Ser598Phe missense_variant 8/101 NM_002419.4 P1Q16584-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1460562
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
726622
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000758
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 14, 2023The c.1793C>T (p.S598F) alteration is located in exon 8 (coding exon 8) of the MAP3K11 gene. This alteration results from a C to T substitution at nucleotide position 1793, causing the serine (S) at amino acid position 598 to be replaced by a phenylalanine (F). 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
0.11
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.45
T;T;.
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Benign
0.58
D
LIST_S2
Benign
0.72
T;T;T
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.31
T;T;T
MetaSVM
Benign
-0.36
T
MutationAssessor
Benign
1.2
L;.;.
MutationTaster
Benign
0.99
D;D;N
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-2.4
N;D;N
REVEL
Uncertain
0.30
Sift
Uncertain
0.0010
D;D;D
Sift4G
Uncertain
0.045
D;D;T
Polyphen
0.99
D;.;.
Vest4
0.45
MutPred
0.12
Loss of glycosylation at S598 (P = 0.0046);.;.;
MVP
0.90
MPC
0.45
ClinPred
0.87
D
GERP RS
5.0
Varity_R
0.14
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1003478674; hg19: chr11-65373270; API