chr8-143718267-A-C

Position:

• chr8-143718267-A-C

Variant summary

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

The NM_139021.3(MAPK15):​c.251A>C​(p.Asn84Thr) 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: 5.00

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]

(HGNC:):

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.251A>C	p.Asn84Thr	missense_variant	4/14	ENST00000338033.9	NP_620590.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK15	ENST00000338033.9	c.251A>C	p.Asn84Thr	missense_variant	4/14	1	NM_139021.3	ENSP00000337691	P1
	ENST00000527908.1	n.278T>G		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

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

Oct 05, 2021

The c.251A>C (p.N84T) alteration is located in exon 4 (coding exon 4) of the MAPK15 gene. This alteration results from a A to C substitution at nucleotide position 251, causing the asparagine (N) at amino acid position 84 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	Uncertain	0.52
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T;.;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	.;D;D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	-0.26	N;N;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-5.5	D;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.012	D;D;D
Sift4G	Uncertain	0.0030	D;T;T
Polyphen		0.98	D;.;.
Vest4		0.68
MutPred		0.39		Gain of phosphorylation at N84 (P = 0.0534);Gain of phosphorylation at N84 (P = 0.0534);Gain of phosphorylation at N84 (P = 0.0534);
MVP		0.68
MPC		0.18
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.32
gMVP		0.60

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: chr8-144800437;