Variant 22-50603464-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_012324.6(MAPK8IP2):c.413C>A(p.Pro138His) variant causes a missense 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAPK8IP2
NM_012324.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

Variant links:

Genes affected

MAPK8IP2 (HGNC:6883): (mitogen-activated protein kinase 8 interacting protein 2) This gene encodes a scaffold protein that is thought to be involved in the regulation of the c-Jun amino-terminal kinase signaling pathway. This protein has been shown to interact with and regulate the activity of MAPK8/JNK1 and MAP2K7/MKK7 kinases. [provided by RefSeq, Jun 2017]

MAPK8IP2 links:

MAPK8IP2 (HGNC:):

MAPK8IP2 links:

Genome browser will be placed here

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;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.877

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK8IP2	NM_012324.6 linkuse as main transcript	c.413C>A	p.Pro138His	missense_variant	3/12	ENST00000329492.6	NP_036456.1	Q13387-1
MAPK8IP2	XM_011530679.3 linkuse as main transcript	c.413C>A	p.Pro138His	missense_variant	3/12		XP_011528981.1
MAPK8IP2	XM_011530680.3 linkuse as main transcript	c.413C>A	p.Pro138His	missense_variant	3/12		XP_011528982.1
MAPK8IP2	XM_011530681.3 linkuse as main transcript	c.413C>A	p.Pro138His	missense_variant	3/12		XP_011528983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK8IP2	ENST00000329492.6 linkuse as main transcript	c.413C>A	p.Pro138His	missense_variant	3/12	1	NM_012324.6	ENSP00000330572.4		Q13387-1
MAPK8IP2	ENST00000008876.7 linkuse as main transcript	n.332C>A		non_coding_transcript_exon_variant	1/10	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1414188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696600

Gnomad4 AFR exome

AF:

0.00

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

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2024

The c.413C>A (p.P138H) alteration is located in exon 3 (coding exon 3) of the MAPK8IP2 gene. This alteration results from a C to A substitution at nucleotide position 413, causing the proline (P) at amino acid position 138 to be replaced by a histidine (H). 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

Pathogenic

0.63

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.73

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.69

M_CAP

Pathogenic

0.35

MetaRNN

Pathogenic

0.88

MetaSVM

Uncertain

0.30

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-4.9

REVEL

Uncertain

0.50

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.78

MutPred

0.36

Loss of glycosylation at P138 (P = 0.0384);

MVP

0.84

ClinPred

1.0

GERP RS

4.6

Varity_R

0.27

gMVP

0.44

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