Variant 15-41775365-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_014994.3(MAPKBP1):c.90C>A(p.Asn30Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MAPKBP1
NM_014994.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.12

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MAPKBP1. . Gene score misZ 2.3719 (greater than the threshold 3.09). Trascript score misZ 3.2144 (greater than threshold 3.09). GenCC has associacion of gene with late-onset nephronophthisis, nephronophthisis 20, nephronophthisis 1.

BP4

Computational evidence support a benign effect (MetaRNN=0.13810474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPKBP1	NM_014994.3 linkuse as main transcript	c.90C>A	p.Asn30Lys	missense_variant	2/31	ENST00000457542.7	NP_055809.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPKBP1	ENST00000457542.7 linkuse as main transcript	c.90C>A	p.Asn30Lys	missense_variant	2/31	1	NM_014994.3	ENSP00000397570	P4	O60336-6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.90C>A (p.N30K) alteration is located in exon 2 (coding exon 1) of the MAPKBP1 gene. This alteration results from a C to A substitution at nucleotide position 90, causing the asparagine (N) at amino acid position 30 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.0080

.;T;.;.;.

Eigen

Benign

0.045

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.87

D;D;D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.14

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N;N;.;.

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.0

N;N;N;N;.

REVEL

Benign

0.032

Sift

Benign

0.37

T;T;T;T;.

Sift4G

Benign

0.42

T;T;T;T;D

Polyphen

0.043

B;B;B;.;.

Vest4

0.17

MutPred

0.45

Gain of methylation at N30 (P = 0.0176);Gain of methylation at N30 (P = 0.0176);Gain of methylation at N30 (P = 0.0176);Gain of methylation at N30 (P = 0.0176);Gain of methylation at N30 (P = 0.0176);

MVP

0.34

MPC

0.84

ClinPred

0.21

GERP RS

4.3

Varity_R

0.14

gMVP

0.66

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over