18-50664070-G-C

Variant names:

• chr18-50664070-G-C
• rs3752087
• NM_002747.4:c.112G>C

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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. V38M) has been classified as Uncertain significance.

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

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002747.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK4	NM_002747.4	MANE Select	c.112G>C	p.Val38Leu	missense	Exon 2 of 6	NP_002738.2
	MAPK4	NM_001292040.2		c.112G>C	p.Val38Leu	missense	Exon 2 of 4	NP_001278969.1
	MAPK4	NM_001292039.2		c.-87-51009G>C		intron	N/A	NP_001278968.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK4	ENST00000400384.7	TSL:1 MANE Select	c.112G>C	p.Val38Leu	missense	Exon 2 of 6	ENSP00000383234.1
	MAPK4	ENST00000588540.1	TSL:1	c.112G>C	p.Val38Leu	missense	Exon 2 of 3	ENSP00000465661.1
	MAPK4	ENST00000592595.5	TSL:1	c.112G>C	p.Val38Leu	missense	Exon 2 of 4	ENSP00000466233.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 55516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.32	N
PhyloP100		0.14
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.036
Sift	Benign	0.23	T
Sift4G	Benign	0.32	T
Polyphen		0.0010	B
Vest4		0.059
MutPred		0.22		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
Mutation Taster		=98/2	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: rs3752087; hg19: chr18-48190440;