MAPKBP1 p.Arg1459*

Variant names:

• chr15-41825474-C-T
• rs751821100
• NM_014994.3:c.*38C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-41825474-C-T
• chr15-41825284-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014994.3(MAPKBP1):​c.*38C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000022 in 1,363,872 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: MAPKBP1 NM_014994.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• 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: ClinGen, Labcorp Genetics (formerly Invitae)
• late-onset nephronophthisis

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000250379 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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.*38C>T		3_prime_UTR	Exon 31 of 31	NP_055809.2	O60336-6
	MAPKBP1	NM_001128608.2		c.*38C>T		3_prime_UTR	Exon 32 of 32	NP_001122080.1	O60336-1
	MAPKBP1	NM_001265611.2		c.*38C>T		3_prime_UTR	Exon 30 of 30	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.*38C>T		3_prime_UTR	Exon 31 of 31	ENSP00000397570.2	O60336-6
	MAPKBP1	ENST00000456763.6	TSL:1	c.*38C>T		3_prime_UTR	Exon 32 of 32	ENSP00000393099.2	O60336-1
	MAPKBP1	ENST00000514566.5	TSL:1	c.*38C>T		3_prime_UTR	Exon 30 of 30	ENSP00000426154.1	O60336-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000128 AC: 2 AN: 156008 AF XY: 0.0000241

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000159

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000220 AC: 3 AN: 1363872 Hom.: 0 Cov.: 25 AF XY: 0.00000299 AC XY: 2 AN XY: 668574

African (AFR) AF: 0.00 AC: 0 AN: 31366

American (AMR) AF: 0.00 AC: 0 AN: 36206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23446

East Asian (EAS) AF: 0.0000275 AC: 1 AN: 36326

South Asian (SAS) AF: 0.0000131 AC: 1 AN: 76312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5382

European-Non Finnish (NFE) AF: 9.53e-7 AC: 1 AN: 1049500

Other (OTH) AF: 0.00 AC: 0 AN: 56518

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.53
PhyloP100		-0.19

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

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

Other links and lift over

dbSNP: rs751821100;

hg19: chr15-42117672;