Variant 8-143719071-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_139021.3(MAPK15):c.496C>G(p.Pro166Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000253 in 1,579,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MAPK15
NM_139021.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.784

Variant links:

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]

MAPK15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055945814).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK15	NM_139021.3 linkuse as main transcript	c.496C>G	p.Pro166Ala	missense_variant	6/14	ENST00000338033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK15	ENST00000338033.9 linkuse as main transcript	c.496C>G	p.Pro166Ala	missense_variant	6/14	1	NM_139021.3	P1	Q8TD08-1
MAPK15	ENST00000395107.8 linkuse as main transcript	c.547C>G	p.Pro183Ala	missense_variant	6/8	1			Q8TD08-3
MAPK15	ENST00000395108.2 linkuse as main transcript	c.496C>G	p.Pro166Ala	missense_variant	6/8	1			Q8TD08-2
MAPK15	ENST00000484654.1 linkuse as main transcript	n.585C>G		non_coding_transcript_exon_variant	6/12	1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000105

AC:

AN:

190180

Hom.:

AF XY:

0.00

AC XY:

AN XY:

102610

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000145

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1427086

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

706958

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000804

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

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 14, 2024

The c.496C>G (p.P166A) alteration is located in exon 6 (coding exon 6) of the MAPK15 gene. This alteration results from a C to G substitution at nucleotide position 496, causing the proline (P) at amino acid position 166 to be replaced by an alanine (A). 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

0.068

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

5.7

DANN

Benign

0.67

DEOGEN2

Benign

0.022

T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.57

.;T;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.056

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.28

N;.;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.057

Sift

Benign

0.61

T;T;T

Sift4G

Benign

0.68

T;T;T

Polyphen

0.014

B;.;.

Vest4

0.14

MutPred

0.46

Loss of disorder (P = 0.1193);.;Loss of disorder (P = 0.1193);

MVP

0.31

MPC

0.028

ClinPred

0.052

GERP RS

2.1

Varity_R

0.064

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over