1-206685320-C-A

Position:

• chr1-206685320-C-A

Variant summary

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

The NM_032960.4(MAPKAPK2):​c.91C>A​(p.Pro31Thr) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAPKAPK2 NM_032960.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.244

Genes affected

MAPKAPK2 (HGNC:6887): (MAPK activated protein kinase 2) This gene encodes a member of the Ser/Thr protein kinase family. This kinase is regulated through direct phosphorylation by p38 MAP kinase. In conjunction with p38 MAP kinase, this kinase is known to be involved in many cellular processes including stress and inflammatory responses, nuclear export, gene expression regulation and cell proliferation. Heat shock protein HSP27 was shown to be one of the substrates of this kinase in vivo. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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=0.11853203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPKAPK2	NM_032960.4	c.91C>A	p.Pro31Thr	missense_variant	1/10	ENST00000367103.4	NP_116584.2
MAPKAPK2	NM_004759.5	c.91C>A	p.Pro31Thr	missense_variant	1/10		NP_004750.1
MAPKAPK2	XM_005273353.4	c.91C>A	p.Pro31Thr	missense_variant	1/11		XP_005273410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPKAPK2	ENST00000367103.4	c.91C>A	p.Pro31Thr	missense_variant	1/10	1	NM_032960.4	ENSP00000356070	P1
MAPKAPK2	ENST00000294981.8	c.91C>A	p.Pro31Thr	missense_variant	1/10	1		ENSP00000294981

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1236108 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 612710

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

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

Sep 25, 2023

The c.91C>A (p.P31T) alteration is located in exon 1 (coding exon 1) of the MAPKAPK2 gene. This alteration results from a C to A substitution at nucleotide position 91, causing the proline (P) at amino acid position 31 to be replaced by a threonine (T). 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	0.070
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.086	.;T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.48	T;T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.33	N;N
REVEL	Benign	0.047
Sift	Benign	0.50	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.0	B;B
Vest4		0.14
MutPred		0.29		Gain of phosphorylation at P31 (P = 0.0059);Gain of phosphorylation at P31 (P = 0.0059);
MVP		0.49
MPC		1.1
ClinPred		0.032	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.055
gMVP		0.29

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: chr1-206858665;