6-136712568-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005923.4(MAP3K5):​c.589-7435A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 151,988 control chromosomes in the GnomAD database, including 23,749 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 0.55 ( 23749 hom., cov: 32)

Consequence

MAP3K5
NM_005923.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.19
Variant links:
Genes affected
MAP3K5 (HGNC:6857): (mitogen-activated protein kinase kinase kinase 5) Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. MAPKKK5 contains 1,374 amino acids with all 11 kinase subdomains. Northern blot analysis shows that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. The MAPKKK5 protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) during transient expression in COS and 293 cells; MAPKKK5 does not activate MAPK/ERK. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAP3K5NM_005923.4 linkc.589-7435A>G intron_variant ENST00000359015.5 NP_005914.1 Q99683-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAP3K5ENST00000359015.5 linkc.589-7435A>G intron_variant 1 NM_005923.4 ENSP00000351908.4 Q99683-1
MAP3K5ENST00000698928.1 linkc.916-7435A>G intron_variant ENSP00000514039.1 A0A8V8TMH5

Frequencies

GnomAD3 genomes
AF:
0.551
AC:
83647
AN:
151868
Hom.:
23690
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.676
Gnomad AMI
AF:
0.677
Gnomad AMR
AF:
0.434
Gnomad ASJ
AF:
0.467
Gnomad EAS
AF:
0.483
Gnomad SAS
AF:
0.383
Gnomad FIN
AF:
0.582
Gnomad MID
AF:
0.516
Gnomad NFE
AF:
0.516
Gnomad OTH
AF:
0.527
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.551
AC:
83765
AN:
151988
Hom.:
23749
Cov.:
32
AF XY:
0.547
AC XY:
40646
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.677
Gnomad4 AMR
AF:
0.433
Gnomad4 ASJ
AF:
0.467
Gnomad4 EAS
AF:
0.483
Gnomad4 SAS
AF:
0.384
Gnomad4 FIN
AF:
0.582
Gnomad4 NFE
AF:
0.516
Gnomad4 OTH
AF:
0.531
Alfa
AF:
0.532
Hom.:
3706
Bravo
AF:
0.548
Asia WGS
AF:
0.456
AC:
1589
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.99
CADD
Benign
0.10
DANN
Benign
0.64

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: rs911185; hg19: chr6-137033706; API