chr22-50261239-A-G

Position:

• chr22-50261239-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002969.6(MAPK12):​c.183T>C​(p.Pro61=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 1,575,850 control chromosomes in the GnomAD database, including 451,117 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.74 (41467 hom., cov: 33)
  • Exomes 𝑓: 0.76 (409650 hom.)
• Consequence: MAPK12 NM_002969.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207

Genes affected

MAPK12 (HGNC:6874): (mitogen-activated protein kinase 12) Activation of members of the mitogen-activated protein kinase family is a major mechanism for transduction of extracellular signals. Stress-activated protein kinases are one subclass of MAP kinases. The protein encoded by this gene functions as a signal transducer during differentiation of myoblasts to myotubes. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=0.207 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK12	NM_002969.6	c.183T>C	p.Pro61=	synonymous_variant	2/12	ENST00000215659.13
MAPK12	NM_001303252.3	c.183T>C	p.Pro61=	synonymous_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK12	ENST00000215659.13	c.183T>C	p.Pro61=	synonymous_variant	2/12	1	NM_002969.6	P1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111827 AN: 151804 Hom.: 41428 Cov.: 33

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.759

GnomAD3 exomes AF: 0.738 AC: 140898 AN: 190900 Hom.: 52337 AF XY: 0.737 AC XY: 77308 AN XY: 104886

Gnomad AFR exome AF: 0.685

Gnomad AMR exome AF: 0.733

Gnomad ASJ exome AF: 0.761

Gnomad EAS exome AF: 0.560

Gnomad SAS exome AF: 0.668

Gnomad FIN exome AF: 0.826

Gnomad NFE exome AF: 0.774

Gnomad OTH exome AF: 0.758

GnomAD4 exome AF: 0.757 AC: 1078010 AN: 1423928 Hom.: 409650 Cov.: 46 AF XY: 0.756 AC XY: 533817 AN XY: 706250

Gnomad4 AFR exome AF: 0.674

Gnomad4 AMR exome AF: 0.732

Gnomad4 ASJ exome AF: 0.762

Gnomad4 EAS exome AF: 0.608

Gnomad4 SAS exome AF: 0.666

Gnomad4 FIN exome AF: 0.817

Gnomad4 NFE exome AF: 0.770

Gnomad4 OTH exome AF: 0.744

GnomAD4 genome AF: 0.737 AC: 111926 AN: 151922 Hom.: 41467 Cov.: 33 AF XY: 0.737 AC XY: 54712 AN XY: 74276

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.761

Alfa AF: 0.757 Hom.: 19895

Bravo AF: 0.732

Asia WGS AF: 0.692 AC: 2400 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.73

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: rs2272857; hg19: chr22-50699668; COSMIC: COSV53131872; COSMIC: COSV53131872;