Genetic Variant MAP3K10:p.Thr14Lys (chr19-40192072-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002446.4(MAP3K10):c.41C>A(p.Thr14Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000747 in 1,338,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T14P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

MAP3K10
NM_002446.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11862281).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002446.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K10	NM_002446.4	MANE Select	c.41C>A	p.Thr14Lys	missense	Exon 1 of 10	NP_002437.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAP3K10	ENST00000253055.8	TSL:1 MANE Select	c.41C>A	p.Thr14Lys	missense	Exon 1 of 10	ENSP00000253055.2	Q02779
MAP3K10	ENST00000856942.1		c.41C>A	p.Thr14Lys	missense	Exon 1 of 10	ENSP00000527002.1
MAP3K10	ENST00000941194.1		c.41C>A	p.Thr14Lys	missense	Exon 1 of 10	ENSP00000611253.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.47e-7

AC:

AN:

1338218

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

654664

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29080

American (AMR)

AF:

0.00

AC:

AN:

26580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20348

East Asian (EAS)

AF:

0.00

AC:

AN:

35032

South Asian (SAS)

AF:

0.00

AC:

AN:

69384

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42724

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5320

European-Non Finnish (NFE)

AF:

9.49e-7

AC:

AN:

1054252

Other (OTH)

AF:

0.00

AC:

AN:

55498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.14

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.52

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

PhyloP100

1.4

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.5

REVEL

Benign

0.10

Sift

Benign

0.074

Sift4G

Uncertain

0.058

Polyphen

0.057

Vest4

0.13

MutPred

0.40

Gain of ubiquitination at T14 (P = 0.0104)

MVP

0.67

MPC

1.0

ClinPred

0.28

GERP RS

3.1

Varity_R

0.12

gMVP

0.20

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over