NM_002401.5:c.167+1261C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002401.5(MAP3K3):​c.167+1261C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,128 control chromosomes in the GnomAD database, including 14,312 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.38 ( 14312 hom., cov: 32)

Consequence

MAP3K3
NM_002401.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.316

Publications

15 publications found
Variant links:
Genes affected
MAP3K3 (HGNC:6855): (mitogen-activated protein kinase kinase kinase 3) This gene product is a 626-amino acid polypeptide that is 96.5% identical to mouse Mekk3. Its catalytic domain is closely related to those of several other kinases, including mouse Mekk2, tobacco NPK, and yeast Ste11. Northern blot analysis revealed a 4.6-kb transcript that appears to be ubiquitously expressed. This protein directly regulates the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by activating SEK and MEK1/2 respectively; it does not regulate the p38 pathway. In cotransfection assays, it enhanced transcription from a nuclear factor kappa-B (NFKB)-dependent reporter gene, consistent with a role in the SAPK pathway. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAP3K3NM_002401.5 linkc.167+1261C>T intron_variant Intron 3 of 15 ENST00000361733.8 NP_002392.2 Q99759-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAP3K3ENST00000361733.8 linkc.167+1261C>T intron_variant Intron 3 of 15 1 NM_002401.5 ENSP00000354485.4 Q99759-1

Frequencies

GnomAD3 genomes
AF:
0.379
AC:
57576
AN:
152010
Hom.:
14259
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.710
Gnomad AMI
AF:
0.267
Gnomad AMR
AF:
0.248
Gnomad ASJ
AF:
0.281
Gnomad EAS
AF:
0.0557
Gnomad SAS
AF:
0.168
Gnomad FIN
AF:
0.205
Gnomad MID
AF:
0.380
Gnomad NFE
AF:
0.281
Gnomad OTH
AF:
0.348
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.379
AC:
57673
AN:
152128
Hom.:
14312
Cov.:
32
AF XY:
0.369
AC XY:
27485
AN XY:
74394
show subpopulations
African (AFR)
AF:
0.711
AC:
29484
AN:
41476
American (AMR)
AF:
0.248
AC:
3789
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.281
AC:
974
AN:
3472
East Asian (EAS)
AF:
0.0558
AC:
289
AN:
5180
South Asian (SAS)
AF:
0.166
AC:
802
AN:
4830
European-Finnish (FIN)
AF:
0.205
AC:
2172
AN:
10584
Middle Eastern (MID)
AF:
0.391
AC:
115
AN:
294
European-Non Finnish (NFE)
AF:
0.281
AC:
19079
AN:
67980
Other (OTH)
AF:
0.344
AC:
726
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1505
3011
4516
6022
7527
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
486
972
1458
1944
2430
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.313
Hom.:
11711
Bravo
AF:
0.398
Asia WGS
AF:
0.162
AC:
566
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
7.8
DANN
Benign
0.38
PhyloP100
0.32
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs8081612; hg19: chr17-61724695; API