22-50261239-A-G

Variant names:

• chr22-50261239-A-G
• rs2272857
• NM_002969.6:c.183T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002969.6(MAPK12):​c.183T>C​(p.Pro61Pro) 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
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002969.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK12	NM_002969.6	MANE Select	c.183T>C	p.Pro61Pro	synonymous	Exon 2 of 12	NP_002960.2
	MAPK12	NM_001303252.3		c.183T>C	p.Pro61Pro	synonymous	Exon 2 of 11	NP_001290181.1	P53778-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK12	ENST00000215659.13	TSL:1 MANE Select	c.183T>C	p.Pro61Pro	synonymous	Exon 2 of 12	ENSP00000215659.8	P53778-1
	MAPK12	ENST00000622558.4	TSL:1	c.183T>C	p.Pro61Pro	synonymous	Exon 2 of 11	ENSP00000479972.1	P53778-2
	MAPK12	ENST00000395778.3	TSL:1	c.183T>C	p.Pro61Pro	synonymous	Exon 2 of 4	ENSP00000379124.3	A8MY48

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

GnomAD2 exomes AF: 0.738 AC: 140898 AN: 190900 AF XY: 0.737

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 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

African (AFR) AF: 0.674 AC: 20883 AN: 30976

American (AMR) AF: 0.732 AC: 29984 AN: 40936

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 19270 AN: 25280

East Asian (EAS) AF: 0.608 AC: 22129 AN: 36410

South Asian (SAS) AF: 0.666 AC: 54156 AN: 81340

European-Finnish (FIN) AF: 0.817 AC: 40614 AN: 49694

Middle Eastern (MID) AF: 0.756 AC: 4279 AN: 5660

European-Non Finnish (NFE) AF: 0.770 AC: 842929 AN: 1094838

Other (OTH) AF: 0.744 AC: 43766 AN: 58794

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

African (AFR) AF: 0.683 AC: 28309 AN: 41462

American (AMR) AF: 0.733 AC: 11207 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2667 AN: 3472

East Asian (EAS) AF: 0.574 AC: 2940 AN: 5124

South Asian (SAS) AF: 0.654 AC: 3160 AN: 4830

European-Finnish (FIN) AF: 0.828 AC: 8732 AN: 10552

Middle Eastern (MID) AF: 0.760 AC: 222 AN: 292

European-Non Finnish (NFE) AF: 0.770 AC: 52275 AN: 67882

Other (OTH) AF: 0.761 AC: 1606 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.73
PhyloP100		0.21
PromoterAI		-0.073	Neutral
Mutation Taster		=293/7	polymorphism (auto)

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