chr8-143719362-A-G

Position:

• chr8-143719362-A-G

Variant summary

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

The NM_139021.3(MAPK15):​c.601A>G​(p.Met201Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAPK15 NM_139021.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.21

Genes affected

MAPK15 (HGNC:24667): (mitogen-activated protein kinase 15) Enables MAP kinase activity and chromatin binding activity. Involved in several processes, including dopamine uptake; positive regulation of DNA metabolic process; and regulation of organelle organization. Located in several cellular components, including Golgi apparatus; autophagosome; and microtubule organizing center. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK15	NM_139021.3	c.601A>G	p.Met201Val	missense_variant	7/14	ENST00000338033.9	NP_620590.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK15	ENST00000338033.9	c.601A>G	p.Met201Val	missense_variant	7/14	1	NM_139021.3	ENSP00000337691	P1
MAPK15	ENST00000395107.8	c.652A>G	p.Met218Val	missense_variant	7/8	1		ENSP00000378539
MAPK15	ENST00000395108.2	c.601A>G	p.Met201Val	missense_variant	7/8	1		ENSP00000378540
MAPK15	ENST00000484654.1	n.690A>G		non_coding_transcript_exon_variant	7/12	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 42

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

Mar 15, 2024

The c.601A>G (p.M201V) alteration is located in exon 7 (coding exon 7) of the MAPK15 gene. This alteration results from a A to G substitution at nucleotide position 601, causing the methionine (M) at amino acid position 201 to be replaced by a valine (V). 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	0.15
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Benign	0.89
DEOGEN2	Benign	0.12	T;.;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	.;T;T
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.68	N;.;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.8	D;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.027	D;T;T
Sift4G	Uncertain	0.010	D;T;T
Polyphen		0.21	B;.;.
Vest4		0.53
MutPred		0.43		Gain of catalytic residue at M201 (P = 0.0146);.;Gain of catalytic residue at M201 (P = 0.0146);
MVP		0.62
MPC		0.026
ClinPred		0.86	D
GERP RS		1.6
Varity_R		0.48
gMVP		0.74

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: chr8-144801532;