Variant 19-40192087-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002446.4(MAP3K10):c.56C>T(p.Pro19Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAP3K10
NM_002446.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62

Variant links:

Genes affected

MAP3K10 (HGNC:6849): (mitogen-activated protein kinase kinase kinase 10) The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase has been shown to activate MAPK8/JNK and MKK4/SEK1, and this kinase itself can be phoshorylated, and thus activated by JNK kinases. This kinase functions preferentially on the JNK signaling pathway, and is reported to be involved in nerve growth factor (NGF) induced neuronal apoptosis. [provided by RefSeq, Jul 2008]

MAP3K10 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19174072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K10	NM_002446.4 link	c.56C>T	p.Pro19Leu	missense_variant	1/10	ENST00000253055.8	NP_002437.2	Q02779
MAP3K10	XM_011526981.3 link	c.56C>T	p.Pro19Leu	missense_variant	1/10		XP_011525283.1
MAP3K10	XM_011526982.4 link	c.56C>T	p.Pro19Leu	missense_variant	1/10		XP_011525284.1
MAP3K10	XM_047438844.1 link	c.56C>T	p.Pro19Leu	missense_variant	1/9		XP_047294800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K10	ENST00000253055.8 link	c.56C>T	p.Pro19Leu	missense_variant	1/10	1	NM_002446.4	ENSP00000253055.2		Q02779

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1367500

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

672186

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

Sep 30, 2021

The c.56C>T (p.P19L) alteration is located in exon 1 (coding exon 1) of the MAP3K10 gene. This alteration results from a C to T substitution at nucleotide position 56, causing the proline (P) at amino acid position 19 to be replaced by a leucine (L). 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

0.083

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.56

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.062

Sift

Uncertain

0.018

Sift4G

Uncertain

0.020

Polyphen

0.0030

Vest4

0.15

MutPred

0.56

Gain of catalytic residue at P19 (P = 0.0026);

MVP

0.41

MPC

0.87

ClinPred

0.80

GERP RS

2.1

Varity_R

0.41

gMVP

0.46

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