chr8-143719026-G-C

Position:

• chr8-143719026-G-C

Variant summary

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

The NM_139021.3(MAPK15):​c.451G>C​(p.Val151Leu) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MAPK15 NM_139021.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25378886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK15	NM_139021.3	c.451G>C	p.Val151Leu	missense_variant	6/14	ENST00000338033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK15	ENST00000338033.9	c.451G>C	p.Val151Leu	missense_variant	6/14	1	NM_139021.3	P1
MAPK15	ENST00000395107.8	c.502G>C	p.Val168Leu	missense_variant	6/8	1
MAPK15	ENST00000395108.2	c.451G>C	p.Val151Leu	missense_variant	6/8	1
MAPK15	ENST00000484654.1	n.540G>C		non_coding_transcript_exon_variant	6/12	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 31

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

Jan 22, 2024

The c.451G>C (p.V151L) alteration is located in exon 6 (coding exon 6) of the MAPK15 gene. This alteration results from a G to C substitution at nucleotide position 451, causing the valine (V) at amino acid position 151 to be replaced by a leucine (L). 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	0.34
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Benign	0.87
DEOGEN2	Benign	0.071	T;.;.
Eigen	Benign	-0.0041
Eigen_PC	Benign	0.056
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.97	.;D;D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.23	N;.;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.4	N;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.017	D;T;T
Sift4G	Uncertain	0.011	D;T;T
Polyphen		0.87	P;.;.
Vest4		0.28
MutPred		0.66		Loss of catalytic residue at V151 (P = 0.0051);.;Loss of catalytic residue at V151 (P = 0.0051);
MVP		0.42
MPC		0.17
ClinPred		0.86	D
GERP RS		4.0
Varity_R		0.33
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr8-144801196;