chr19-40213169-T-G

Variant names:

• chr19-40213169-T-G
• rs1129156
• NM_002446.4:c.1818T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002446.4(MAP3K10):​c.1818T>G​(p.Phe606Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAP3K10 NM_002446.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 24 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K10	NM_002446.4	c.1818T>G	p.Phe606Leu	missense_variant	Exon 8 of 10	ENST00000253055.8	NP_002437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K10	ENST00000253055.8	c.1818T>G	p.Phe606Leu	missense_variant	Exon 8 of 10	1	NM_002446.4	ENSP00000253055.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	9.9
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.085	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.55	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		-0.28
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.31
Sift	Benign	0.063	T
Sift4G	Benign	0.17	T
Polyphen		0.17	B
Vest4		0.59
MutPred		0.24		Loss of glycosylation at S608 (P = 0.1975);
MVP		0.71
MPC		1.1
ClinPred		0.99	D
GERP RS		0.50
Varity_R		0.39
gMVP		0.22
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs1129156; hg19: chr19-40719076;