rs2237262

Variant summary

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

The ENST00000359015.5(MAP3K5):​c.3761+1435G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,058 control chromosomes in the GnomAD database, including 3,452 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 0.20 ( 3452 hom., cov: 32)

Consequence

MAP3K5
ENST00000359015.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.632
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAP3K5NM_005923.4 linkuse as main transcriptc.3761+1435G>C intron_variant ENST00000359015.5 NP_005914.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAP3K5ENST00000359015.5 linkuse as main transcriptc.3761+1435G>C intron_variant 1 NM_005923.4 ENSP00000351908 P1Q99683-1
MAP3K5ENST00000698928.1 linkuse as main transcriptc.4088+1435G>C intron_variant ENSP00000514039

Frequencies

GnomAD3 genomes
AF:
0.196
AC:
29844
AN:
151940
Hom.:
3439
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.277
Gnomad AMI
AF:
0.292
Gnomad AMR
AF:
0.227
Gnomad ASJ
AF:
0.149
Gnomad EAS
AF:
0.411
Gnomad SAS
AF:
0.134
Gnomad FIN
AF:
0.110
Gnomad MID
AF:
0.142
Gnomad NFE
AF:
0.143
Gnomad OTH
AF:
0.207
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.197
AC:
29902
AN:
152058
Hom.:
3452
Cov.:
32
AF XY:
0.195
AC XY:
14461
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.278
Gnomad4 AMR
AF:
0.226
Gnomad4 ASJ
AF:
0.149
Gnomad4 EAS
AF:
0.411
Gnomad4 SAS
AF:
0.135
Gnomad4 FIN
AF:
0.110
Gnomad4 NFE
AF:
0.143
Gnomad4 OTH
AF:
0.211
Alfa
AF:
0.166
Hom.:
316
Bravo
AF:
0.211
Asia WGS
AF:
0.294
AC:
1021
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.51
DANN
Benign
0.21

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: rs2237262; hg19: chr6-136887334; API