dbSNP rs5880308: MAP3K5:c.96+84_96+103delCGGCGCGGCGCGGCGCGGCG (chr6-136792541-CCGCCGCGCCGCGCCGCGCCG-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001438058.1(MAP3K5):c.96+84_96+103delCGGCGCGGCGCGGCGCGGCG variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAP3K5
NM_001438058.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.332

Publications

2 publications found

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]

MAP3K5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438058.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MAP3K5	NM_001438058.1		c.96+84_96+103delCGGCGCGGCGCGGCGCGGCG	intron	N/A	NP_001424987.1
MAP3K5	NM_005923.4	MANE Select	c.-404_-385delCGGCGCGGCGCGGCGCGGCG	upstream_gene	N/A	NP_005914.1
MAP3K5	NM_001438579.1		c.-846_-827delCGGCGCGGCGCGGCGCGGCG	upstream_gene	N/A	NP_001425508.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MAP3K5	ENST00000698928.1		c.96+84_96+103delCGGCGCGGCGCGGCGCGGCG	intron	N/A	ENSP00000514039.1
MAP3K5	ENST00000359015.5	TSL:1 MANE Select	c.-404_-385delCGGCGCGGCGCGGCGCGGCG	upstream_gene	N/A	ENSP00000351908.4
MAP3K5	ENST00000954598.1		c.-404_-385delCGGCGCGGCGCGGCGCGGCG	upstream_gene	N/A	ENSP00000624657.1

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

148984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000663

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

16164

Hom.:

AF XY:

0.00

AC XY:

AN XY:

7930

African (AFR)

AF:

0.00

AC:

AN:

266

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

492

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

14610

Other (OTH)

AF:

0.00

AC:

AN:

538

GnomAD4 genome

AF:

0.0000134

AC:

AN:

148984

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72596

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40622

American (AMR)

AF:

0.0000663

AC:

AN:

15088

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.00

AC:

AN:

4928

South Asian (SAS)

AF:

0.00

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9930

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

66942

Other (OTH)

AF:

0.00

AC:

AN:

2046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

806

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.33

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over