19-40192036-A-T

Position:

• chr19-40192036-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002446.4(MAP3K10):​c.5A>T​(p.Glu2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAP3K10 NM_002446.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.17

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K10	NM_002446.4	c.5A>T	p.Glu2Val	missense_variant	1/10	ENST00000253055.8	NP_002437.2
MAP3K10	XM_011526981.3	c.5A>T	p.Glu2Val	missense_variant	1/10		XP_011525283.1
MAP3K10	XM_011526982.4	c.5A>T	p.Glu2Val	missense_variant	1/10		XP_011525284.1
MAP3K10	XM_047438844.1	c.5A>T	p.Glu2Val	missense_variant	1/9		XP_047294800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K10	ENST00000253055.8	c.5A>T	p.Glu2Val	missense_variant	1/10	1	NM_002446.4	ENSP00000253055.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2024

The c.5A>T (p.E2V) alteration is located in exon 1 (coding exon 1) of the MAP3K10 gene. This alteration results from a A to T substitution at nucleotide position 5, causing the glutamic acid (E) at amino acid position 2 to be replaced by a valine (V). 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	0.19
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.32	T
M_CAP	Pathogenic	0.61	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.011	D
Polyphen		0.95	P
Vest4		0.28
MutPred		0.22		Loss of disorder (P = 0.1271);
MVP		0.85
MPC		1.9
ClinPred		0.67	D
GERP RS		4.2
Varity_R		0.24
gMVP		0.31

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.

Other links and lift over

hg19: chr19-40697943;