15-41810717-CAAAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr15-41810717-C-CAAAAAAA
• rs58612719
• NM_014994.3:c.207-150_207-144dupAAAAAAA

Variant summary

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

The NM_014994.3(MAPKBP1):​c.207-150_207-144dupAAAAAAA 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 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000058 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAPKBP1 NM_014994.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.616
• Publications: 0 publications found

Genes affected

MAPKBP1 (HGNC:29536): (mitogen-activated protein kinase binding protein 1) This gene encodes a scaffold protein that regulates the JNK (c-Jun N-terminal kinase) and NOD2 (nucleotide-binding oligomerization domain-containing protein 2) signaling pathways. The encoded protein interacts with another related JNK pathway scaffold protein, WDR62, via a conserved dimerization domain, and enhances JNK signaling. This protein may play a role in bacterial immunity by binding to the NOD2 receptor and negatively regulating downstream antibacterial and pro-inflammatory signaling. Mutations in this gene that impair cellular localization of the encoded protein cause a form of nephronophthisis, an autosomal-recessive kidney disorder, in human patients. [provided by RefSeq, May 2017]

MAPKBP1 Gene-Disease associations (from GenCC):

• nephronophthisis 20

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• late-onset nephronophthisis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nephronophthisis 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014994.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKBP1	NM_014994.3	MANE Select	c.207-150_207-144dupAAAAAAA		intron	N/A	NP_055809.2	O60336-6
	MAPKBP1	NM_001128608.2		c.207-150_207-144dupAAAAAAA		intron	N/A	NP_001122080.1	O60336-1
	MAPKBP1	NM_001265611.2		c.207-150_207-144dupAAAAAAA		intron	N/A	NP_001252540.1	O60336-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKBP1	ENST00000457542.7	TSL:1 MANE Select	c.207-150_207-144dupAAAAAAA		intron	N/A	ENSP00000397570.2	O60336-6
	MAPKBP1	ENST00000456763.6	TSL:1	c.207-150_207-144dupAAAAAAA		intron	N/A	ENSP00000393099.2	O60336-1
	MAPKBP1	ENST00000514566.5	TSL:1	c.207-150_207-144dupAAAAAAA		intron	N/A	ENSP00000426154.1	O60336-2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 84082 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000575 AC: 2 AN: 347806 Hom.: 0 Cov.: 0 AF XY: 0.0000109 AC XY: 2 AN XY: 183564

African (AFR) AF: 0.00 AC: 0 AN: 9926

American (AMR) AF: 0.00 AC: 0 AN: 13540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10422

East Asian (EAS) AF: 0.00 AC: 0 AN: 22104

South Asian (SAS) AF: 0.00 AC: 0 AN: 35886

European-Finnish (FIN) AF: 0.0000783 AC: 2 AN: 25554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1506

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 209030

Other (OTH) AF: 0.00 AC: 0 AN: 19838

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 84082 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 38868

African (AFR) AF: 0.00 AC: 0 AN: 23272

American (AMR) AF: 0.00 AC: 0 AN: 7712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2218

East Asian (EAS) AF: 0.00 AC: 0 AN: 2692

South Asian (SAS) AF: 0.00 AC: 0 AN: 2396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 174

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 41364

Other (OTH) AF: 0.00 AC: 0 AN: 1096

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.62

Splicing

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

Other links and lift over

dbSNP: rs58612719; hg19: chr15-42102915;