rs55800528

Variant names:

• chr18-50664141-C-G
• NM_002747.4:c.183C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-50664141-C-G
• chr18-50664141-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002747.4(MAPK4):​c.183C>G​(p.His61Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H61H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MAPK4 NM_002747.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3868485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK4	NM_002747.4	c.183C>G	p.His61Gln	missense_variant	Exon 2 of 6	ENST00000400384.7	NP_002738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK4	ENST00000400384.7	c.183C>G	p.His61Gln	missense_variant	Exon 2 of 6	1	NM_002747.4	ENSP00000383234.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461846 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	0.031
DANN	Benign	0.96
DEOGEN2	Benign	0.036	T;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	-0.25	N;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.3	N;.;.
REVEL	Uncertain	0.34
Sift	Benign	0.054	T;.;.
Sift4G	Uncertain	0.052	T;D;D
Polyphen		0.49	P;.;.
Vest4		0.63
MutPred		0.67		Loss of methylation at R57 (P = 0.148);Loss of methylation at R57 (P = 0.148);Loss of methylation at R57 (P = 0.148);
MVP		0.57
MPC		1.6
ClinPred		0.74	D
GERP RS		-8.1
Varity_R		0.27
gMVP		0.65

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: chr18-48190511;