rs1057519305
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP5
The NM_014994.3(MAPKBP1):c.1613G>A(p.Arg538Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,158 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
MAPKBP1
NM_014994.3 missense
NM_014994.3 missense
Scores
10
6
1
Clinical Significance
Conservation
PhyloP100: 10.0
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, MAPKBP1
PP5
?
Variant 15-41816937-G-A is Pathogenic according to our data. Variant chr15-41816937-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 374918.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAPKBP1 | NM_014994.3 | c.1613G>A | p.Arg538Gln | missense_variant | 14/31 | ENST00000457542.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPKBP1 | ENST00000457542.7 | c.1613G>A | p.Arg538Gln | missense_variant | 14/31 | 1 | NM_014994.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459158Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 725602
GnomAD4 exome
AF:
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2
AN:
1459158
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Cov.:
29
AF XY:
AC XY:
1
AN XY:
725602
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
Bravo
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Nephronophthisis 20 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 22, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;D
Vest4
MutPred
0.43
.;Loss of phosphorylation at S543 (P = 0.0825);.;
MVP
MPC
1.9
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at