Genetic Variant MAP3K5:c.96+99_96+103dupCGGCG (chr6-136792541-C-CCGCCG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_001438058.1(MAP3K5):c.96+99_96+103dupCGGCG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0032 ( 2 hom., cov: 0)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

MAP3K5
NM_001438058.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

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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new If you want to explore the variant's impact on the transcript NM_001438058.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00322 (480/149090) while in subpopulation EAS AF = 0.0193 (95/4910). AF 95% confidence interval is 0.0162. There are 2 homozygotes in GnomAd4. There are 263 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 480 AD gene.

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	UniProt
MAP3K5	NM_001438058.1		c.96+99_96+103dupCGGCG	intron	N/A	NP_001424987.1	A0A8V8TMH5
MAP3K5	NM_005923.4	MANE Select	c.-389_-385dupCGGCG	upstream_gene	N/A	NP_005914.1	Q99683-1
MAP3K5	NM_001438579.1		c.-831_-827dupCGGCG	upstream_gene	N/A	NP_001425508.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAP3K5	ENST00000698928.1		c.96+103_96+104insCGGCG	intron	N/A	ENSP00000514039.1	A0A8V8TMH5
MAP3K5	ENST00000359015.5	TSL:1 MANE Select	c.-385_-384insCGGCG	upstream_gene	N/A	ENSP00000351908.4	Q99683-1
MAP3K5	ENST00000954598.1		c.-385_-384insCGGCG	upstream_gene	N/A	ENSP00000624657.1

Frequencies

GnomAD3 genomes

AF:

0.00320

AC:

477

AN:

148980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00378

Gnomad ASJ

AF:

0.0247

Gnomad EAS

AF:

0.0193

Gnomad SAS

AF:

0.00418

Gnomad FIN

AF:

0.00161

Gnomad MID

AF:

0.00323

Gnomad NFE

AF:

0.00205

Gnomad OTH

AF:

0.00391

GnomAD4 exome

AF:

0.0000619

AC:

AN:

16164

Hom.:

Cov.:

AF XY:

0.000126

AC XY:

AN XY:

7930

show subpopulations

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:

0.0000684

AC:

AN:

14610

Other (OTH)

AF:

0.00

AC:

AN:

538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00322

AC:

480

AN:

149090

Hom.:

Cov.:

AF XY:

0.00362

AC XY:

263

AN XY:

72712

show subpopulations

African (AFR)

AF:

0.00150

AC:

AN:

40736

American (AMR)

AF:

0.00377

AC:

AN:

15108

Ashkenazi Jewish (ASJ)

AF:

0.0247

AC:

AN:

3446

East Asian (EAS)

AF:

0.0193

AC:

AN:

4910

South Asian (SAS)

AF:

0.00419

AC:

AN:

4778

European-Finnish (FIN)

AF:

0.00161

AC:

AN:

9928

Middle Eastern (MID)

AF:

0.00345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00205

AC:

137

AN:

66932

Other (OTH)

AF:

0.00386

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00158

Hom.:

806

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over