3-185482377-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_004721.5(MAP3K13):​c.2822C>T​(p.Ser941Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000369 in 1,461,604 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: 0.000037 ( 0 hom. )

Consequence

MAP3K13
NM_004721.5 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.80
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.26961166).
BS2
High AC in GnomAdExome4 at 54 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAP3K13NM_004721.5 linkc.2822C>T p.Ser941Leu missense_variant Exon 14 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.2822C>T p.Ser941Leu missense_variant Exon 14 of 14 1 NM_004721.5 ENSP00000265026.3 O43283-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251426
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000369
AC:
54
AN:
1461604
Hom.:
0
Cov.:
30
AF XY:
0.0000358
AC XY:
26
AN XY:
727120
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000432
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 18, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2822C>T (p.S941L) alteration is located in exon 14 (coding exon 13) of the MAP3K13 gene. This alteration results from a C to T substitution at nucleotide position 2822, causing the serine (S) at amino acid position 941 to be replaced by a leucine (L). 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
0.15
BayesDel_addAF
Benign
-0.019
T
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.065
.;T;.;T
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.87
D;.;D;D
M_CAP
Uncertain
0.29
D
MetaRNN
Benign
0.27
T;T;T;T
MetaSVM
Uncertain
0.57
D
MutationAssessor
Benign
1.0
.;L;.;L
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-2.3
N;N;N;N
REVEL
Uncertain
0.47
Sift
Uncertain
0.016
D;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.34
MutPred
0.25
.;Gain of glycosylation at S945 (P = 0.0155);.;Gain of glycosylation at S945 (P = 0.0155);
MVP
0.74
MPC
0.81
ClinPred
0.64
D
GERP RS
5.0
Varity_R
0.21
gMVP
0.24

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

LitVar

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

Other links and lift over

dbSNP: rs779071892; hg19: chr3-185200165; API