3-185463617-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_004721.5(MAP3K13):c.1346G>A(p.Arg449Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,160 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 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
MAP3K13
NM_004721.5 missense
NM_004721.5 missense
Scores
2
10
5
Clinical Significance
Conservation
PhyloP100: 9.96
Genes affected
MAP3K13 (HGNC:6852): (mitogen-activated protein kinase kinase kinase 13) The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase contains a dual leucine-zipper motif, and has been shown to form dimers/oligomers through its leucine-zipper motif. This kinase can phosphorylate and activate MAPK8/JNK, MAP2K7/MKK7, which suggests a role in the JNK signaling pathway. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PP2
Missense variant where missense usually causes diseases, MAP3K13
BP4
Computational evidence support a benign effect (MetaRNN=0.36182493).
BS2
High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAP3K13 | NM_004721.5 | c.1346G>A | p.Arg449Gln | missense_variant | 8/14 | ENST00000265026.8 | |
LOC124906312 | XR_007096202.1 | n.4273-2752C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAP3K13 | ENST00000265026.8 | c.1346G>A | p.Arg449Gln | missense_variant | 8/14 | 1 | NM_004721.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251430Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135882
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GnomAD4 exome AF: 0.00000890 AC: 13AN: 1460888Hom.: 0 Cov.: 29 AF XY: 0.00000413 AC XY: 3AN XY: 726786
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152272Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74464
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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 submitter | clinical testing | Ambry Genetics | Jun 23, 2023 | The c.1346G>A (p.R449Q) alteration is located in exon 8 (coding exon 7) of the MAP3K13 gene. This alteration results from a G to A substitution at nucleotide position 1346, causing the arginine (R) at amino acid position 449 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
N;D;N;D;N
REVEL
Uncertain
Sift
Benign
D;D;D;D;T
Sift4G
Uncertain
D;D;T;D;T
Polyphen
P;P;P;P;.
Vest4
MVP
MPC
1.0
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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