Variant chr22-50600850-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_012324.6(MAPK8IP2):c.32C>T(p.Ser11Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000977 in 1,310,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000074 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

MAPK8IP2
NM_012324.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23

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:

CHKB (HGNC:):

CHKB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22861004).

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK8IP2	NM_012324.6 linkuse as main transcript	c.32C>T	p.Ser11Phe	missense_variant	1/12	ENST00000329492.6	NP_036456.1	Q13387-1
MAPK8IP2	XM_011530679.3 linkuse as main transcript	c.32C>T	p.Ser11Phe	missense_variant	1/12		XP_011528981.1
MAPK8IP2	XM_011530680.3 linkuse as main transcript	c.32C>T	p.Ser11Phe	missense_variant	1/12		XP_011528982.1
MAPK8IP2	XM_011530681.3 linkuse as main transcript	c.32C>T	p.Ser11Phe	missense_variant	1/12		XP_011528983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK8IP2	ENST00000329492.6 linkuse as main transcript	c.32C>T	p.Ser11Phe	missense_variant	1/12	1	NM_012324.6	ENSP00000330572.4		Q13387-1
CHKB	ENST00000463053.1 linkuse as main transcript	n.306+300G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000742

AC:

AN:

148238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000975

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000105

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000725

AC:

AN:

124060

Hom.:

AF XY:

0.0000143

AC XY:

AN XY:

70158

show subpopulations

Gnomad AFR exome

AF:

0.000252

Gnomad AMR exome

AF:

0.0000536

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000101

AC:

117

AN:

1162324

Hom.:

Cov.:

AF XY:

0.0000974

AC XY:

AN XY:

574956

show subpopulations

Gnomad4 AFR exome

AF:

0.0000452

Gnomad4 AMR exome

AF:

0.0000828

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.0000293

Gnomad4 NFE exome

AF:

0.000110

Gnomad4 OTH exome

AF:

0.0000477

GnomAD4 genome

AF:

0.0000742

AC:

AN:

148346

Hom.:

Cov.:

AF XY:

0.0000692

AC XY:

AN XY:

72300

show subpopulations

Gnomad4 AFR

AF:

0.0000972

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000105

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000124

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000446

AC:

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

May 24, 2023

The c.32C>T (p.S11F) alteration is located in exon 1 (coding exon 1) of the MAPK8IP2 gene. This alteration results from a C to T substitution at nucleotide position 32, causing the serine (S) at amino acid position 11 to be replaced by a phenylalanine (F). 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

0.95

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.34

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.18

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.93

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.34

PROVEAN

Benign

-1.5

REVEL

Benign

0.15

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0050

Polyphen

0.95

Vest4

0.13

MVP

0.63

ClinPred

0.099

GERP RS

3.0

Varity_R

0.19

gMVP

0.54

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over