22-50264995-G-A

Position:

• chr22-50264995-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000330651.11(MAPK11):​c.1048C>T​(p.Pro350Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MAPK11 ENST00000330651.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70

Genes affected

MAPK11 (HGNC:6873): (mitogen-activated protein kinase 11) This gene encodes a member of a family of protein kinases that are involved in the integration of biochemical signals for a wide variety of cellular processes, including cell proliferation, differentiation, transcriptional regulation, and development. The encoded protein can be activated by proinflammatory cytokines and environmental stresses through phosphorylation by mitogen activated protein kinase kinases (MKKs). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.228746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK11	NM_002751.7	c.1048C>T	p.Pro350Ser	missense_variant	12/12	ENST00000330651.11	NP_002742.3
MAPK11	XM_047441447.1	c.724C>T	p.Pro242Ser	missense_variant	10/10		XP_047297403.1
MAPK11	NR_110887.2	n.1136C>T		non_coding_transcript_exon_variant	12/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK11	ENST00000330651.11	c.1048C>T	p.Pro350Ser	missense_variant	12/12	1	NM_002751.7	ENSP00000333685	P1
MAPK11	ENST00000395764.5	c.1048C>T	p.Pro350Ser	missense_variant, NMD_transcript_variant	12/13	1		ENSP00000379113
MAPK11	ENST00000417877.1	c.*560C>T		3_prime_UTR_variant, NMD_transcript_variant	12/12	5		ENSP00000409136

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461046 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726786

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: 0.00

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.1048C>T (p.P350S) alteration is located in exon 12 (coding exon 12) of the MAPK11 gene. This alteration results from a C to T substitution at nucleotide position 1048, causing the proline (P) at amino acid position 350 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.70	D
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.73	D
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	0.88	D
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.034	D
Polyphen		0.0	B
Vest4		0.18
MutPred		0.27		Loss of catalytic residue at P350 (P = 0.001);
MVP		0.82
MPC		0.25
ClinPred		0.80	D
GERP RS		2.0
Varity_R		0.063
gMVP		0.19

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: chr22-50703424;