NM_004721.5:c.2658C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004721.5(MAP3K13):​c.2658C>G​(p.Asp886Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MAP3K13
NM_004721.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.463
Variant links:
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]
TMEM41A (HGNC:30544): (transmembrane protein 41A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05627179).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAP3K13NM_004721.5 linkc.2658C>G p.Asp886Glu missense_variant Exon 13 of 14 ENST00000265026.8 NP_004712.1 O43283-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAP3K13ENST00000265026.8 linkc.2658C>G p.Asp886Glu missense_variant Exon 13 of 14 1 NM_004721.5 ENSP00000265026.3 O43283-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
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
Oct 19, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2658C>G (p.D886E) alteration is located in exon 13 (coding exon 12) of the MAP3K13 gene. This alteration results from a C to G substitution at nucleotide position 2658, causing the aspartic acid (D) at amino acid position 886 to be replaced by a glutamic acid (E). 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
0.090
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
5.5
DANN
Uncertain
0.98
DEOGEN2
Benign
0.029
.;T;.;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.93
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.81
T;.;T;T
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.056
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
.;N;.;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.94
N;N;N;N
REVEL
Benign
0.20
Sift
Benign
0.14
T;T;T;T
Sift4G
Benign
0.45
T;T;T;T
Polyphen
0.0030
B;B;B;B
Vest4
0.098
MutPred
0.22
.;Gain of glycosylation at S890 (P = 0.0336);.;Gain of glycosylation at S890 (P = 0.0336);
MVP
0.36
MPC
0.22
ClinPred
0.28
T
GERP RS
-3.5
Varity_R
0.091
gMVP
0.037

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-185198176; API