NM_001395002.1:c.1694G>T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001395002.1(MAP4K4):c.1694G>T(p.Arg565Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,600,960 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
MAP4K4
NM_001395002.1 missense
NM_001395002.1 missense
Scores
2
9
8
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 8.92
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MAP4K4 | NM_001395002.1 | c.1694G>T | p.Arg565Leu | missense_variant | Exon 15 of 33 | ENST00000324219.9 | NP_001381931.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000276 AC: 4AN: 1448754Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1AN XY: 719178
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74362
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T;T;.;.;T;T;T;.;D;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;.;.;.;.;.;.;L;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;.;D;D;.;D;.;.;.;D;D;D;D
REVEL
Uncertain
Sift
Benign
.;.;T;T;.;T;.;.;.;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.99, 0.97, 0.99
.;.;D;D;D;.;.;.;.;D;D;.;.
Vest4
MutPred
0.24
.;.;.;.;.;.;.;Loss of methylation at R565 (P = 0.0237);.;Loss of methylation at R565 (P = 0.0237);.;.;.;
MVP
MPC
0.70
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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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