2-101698120-G-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001395002.1(MAP4K4):c.40G>T(p.Asp14Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MAP4K4
NM_001395002.1 missense
NM_001395002.1 missense
Scores
7
9
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.16
Genes affected
MAP4K4 (HGNC:6866): (mitogen-activated protein kinase kinase kinase kinase 4) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase has been shown to specifically activate MAPK8/JNK. The activation of MAPK8 by this kinase is found to be inhibited by the dominant-negative mutants of MAP3K7/TAK1, MAP2K4/MKK4, and MAP2K7/MKK7, which suggests that this kinase may function through the MAP3K7-MAP2K4-MAP2K7 kinase cascade, and mediate the TNF-alpha signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.744
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MAP4K4 | NM_001395002.1 | c.40G>T | p.Asp14Tyr | missense_variant | 1/33 | ENST00000324219.9 | NP_001381931.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MAP4K4 | ENST00000324219.9 | c.40G>T | p.Asp14Tyr | missense_variant | 1/33 | 5 | NM_001395002.1 | ENSP00000313644 | P3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1130514Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 560218
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1130514
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
560218
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;T;T;.;.;T;T;.;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
.;M;.;.;.;M;.;.;.;M;.
MutationTaster
Benign
D;D;D;D;D;N;N
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;D;D;D;.;D;.;.;D;D
REVEL
Uncertain
Sift
Uncertain
D;.;D;D;D;.;D;.;.;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D;D;D
Polyphen
1.0, 1.0
.;.;D;D;D;D;.;.;.;D;.
Vest4
0.47, 0.47, 0.57, 0.54, 0.68, 0.68, 0.65, 0.68, 0.66, 0.71
MutPred
Loss of disorder (P = 0.0332);Loss of disorder (P = 0.0332);Loss of disorder (P = 0.0332);Loss of disorder (P = 0.0332);Loss of disorder (P = 0.0332);Loss of disorder (P = 0.0332);Loss of disorder (P = 0.0332);Loss of disorder (P = 0.0332);Loss of disorder (P = 0.0332);Loss of disorder (P = 0.0332);Loss of disorder (P = 0.0332);
MVP
MPC
1.8
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.