6-136792541-CCGCCGCGCCGCGCCGCGCCG-CCGCCGCGCCGCGCCGCGCCGCGCCG

Position:

• chr6-136792541-CCGCCGCGCCGCGCCGCGCCG-CCGCCGCGCCGCGCCGCGCCGCGCCG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000698928.1(MAP3K5):​c.96+103_96+104insCGGCG 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 ENST00000698928.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 480 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K5	XM_011535839.4	c.96+103_96+104insCGGCG		intron_variant			XP_011534141.2
MAP3K5	XM_017010872.2	c.96+103_96+104insCGGCG		intron_variant			XP_016866361.1
MAP3K5	XM_017010873.2	c.96+103_96+104insCGGCG		intron_variant			XP_016866362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K5	ENST00000698928.1	c.96+103_96+104insCGGCG		intron_variant				ENSP00000514039

Frequencies

GnomAD3 genomes AF: 0.00320 AC: 477 AN: 148980 Hom.: 2 Cov.: 0

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: 1 AN: 16164 Hom.: 0 Cov.: 0 AF XY: 0.000126 AC XY: 1 AN XY: 7930

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000684

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00322 AC: 480 AN: 149090 Hom.: 2 Cov.: 0 AF XY: 0.00362 AC XY: 263 AN XY: 72712

Gnomad4 AFR AF: 0.00150

Gnomad4 AMR AF: 0.00377

Gnomad4 ASJ AF: 0.0247

Gnomad4 EAS AF: 0.0193

Gnomad4 SAS AF: 0.00419

Gnomad4 FIN AF: 0.00161

Gnomad4 NFE AF: 0.00205

Gnomad4 OTH AF: 0.00386

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5880308; hg19: chr6-137113679;