16-1706450-C-G

Variant summary

Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong

The NM_001318852.2(MAPK8IP3):​c.111C>G​(p.Tyr37*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

MAPK8IP3
NM_001318852.2 stop_gained

Scores

4
2
1

Clinical Significance

Likely pathogenic criteria provided, multiple submitters, no conflicts P:4

Conservation

PhyloP100: 5.88
Variant links:
Genes affected
MAPK8IP3 (HGNC:6884): (mitogen-activated protein kinase 8 interacting protein 3) The protein encoded by this gene shares similarity with the product of Drosophila syd gene, required for the functional interaction of kinesin I with axonal cargo. Studies of the similar gene in mouse suggested that this protein may interact with, and regulate the activity of numerous protein kinases of the JNK signaling pathway, and thus function as a scaffold protein in neuronal cells. The C. elegans counterpart of this gene is found to regulate synaptic vesicle transport possibly by integrating JNK signaling and kinesin-1 transport. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 18 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 16-1706450-C-G is Pathogenic according to our data. Variant chr16-1706450-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 598741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAPK8IP3NM_001318852.2 linkc.111C>G p.Tyr37* stop_gained Exon 1 of 32 ENST00000610761.2 NP_001305781.1 Q9UPT6A0A087WYG2B7ZMF3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAPK8IP3ENST00000610761.2 linkc.111C>G p.Tyr37* stop_gained Exon 1 of 32 1 NM_001318852.2 ENSP00000481780.1 A0A087WYG2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Neurodevelopmental disorder with or without variable brain abnormalities; NEDBA Pathogenic:3
Oct 02, 2019
SIB Swiss Institute of Bioinformatics
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: curation

This variant is interpreted as a Likely pathogenic for Neurodevelopmental disorder with or without variable brain abnormalities, autosomal dominant. The following ACMG Tag(s) were applied: PM2, PVS1-Strong. -

May 23, 2019
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only

- -

Feb 07, 2019
Institute of Human Genetics, University of Leipzig Medical Center
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was identified as de novo (maternity and paternity confirmed). -

MAPK8IP3-related disorder Pathogenic:1
Oct 11, 2018
Undiagnosed Diseases Network, NIH
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.55
D
BayesDel_noAF
Pathogenic
0.56
CADD
Pathogenic
40
DANN
Uncertain
0.99
Eigen
Pathogenic
0.69
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.99
D
Vest4
0.80
GERP RS
3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs770703007; hg19: chr16-1756451; API