18-50664070-G-C

Position:

• chr18-50664070-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002747.4(MAPK4):​c.112G>C​(p.Val38Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. V38M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAPK4 NM_002747.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144

Genes affected

MAPK4 (HGNC:6878): (mitogen-activated protein kinase 4) Mitogen-activated protein kinase 4 is a member of the mitogen-activated protein kinase family. Tyrosine kinase growth factor receptors activate mitogen-activated protein kinases which then translocate into the nucleus and phosphorylate nuclear targets. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06796086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK4	NM_002747.4	c.112G>C	p.Val38Leu	missense_variant	2/6	ENST00000400384.7	NP_002738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK4	ENST00000400384.7	c.112G>C	p.Val38Leu	missense_variant	2/6	1	NM_002747.4	ENSP00000383234.1
MAPK4	ENST00000588540.1	c.112G>C	p.Val38Leu	missense_variant	2/3	1		ENSP00000465661.1
MAPK4	ENST00000592595.5	c.112G>C	p.Val38Leu	missense_variant	2/4	1		ENSP00000466233.1
MAPK4	ENST00000540640.3	c.-87-51009G>C		intron_variant		2		ENSP00000439231.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.4
DANN	Benign	0.67
DEOGEN2	Benign	0.015	T;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.068	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.32	N;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.74	N;.;.
REVEL	Benign	0.036
Sift	Benign	0.23	T;.;.
Sift4G	Benign	0.32	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.059
MutPred		0.22		Loss of catalytic residue at V38 (P = 0.0176);Loss of catalytic residue at V38 (P = 0.0176);Loss of catalytic residue at V38 (P = 0.0176);
MVP		0.30
MPC		0.58
ClinPred		0.067	T
GERP RS		-4.1
Varity_R		0.17
gMVP		0.45

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

Other links and lift over

dbSNP: rs3752087; hg19: chr18-48190440;