chr8-143718793-T-C

Position:

• chr8-143718793-T-C

Variant summary

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

The NM_139021.3(MAPK15):​c.305T>C​(p.Val102Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: MAPK15 NM_139021.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.60

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	UniProt
MAPK15	NM_139021.3	c.305T>C	p.Val102Ala	missense_variant	5/14	ENST00000338033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK15	ENST00000338033.9	c.305T>C	p.Val102Ala	missense_variant	5/14	1	NM_139021.3	P1
	ENST00000527908.1	n.99A>G		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 40

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 17, 2021

The c.305T>C (p.V102A) alteration is located in exon 5 (coding exon 5) of the MAPK15 gene. This alteration results from a T to C substitution at nucleotide position 305, causing the valine (V) at amino acid position 102 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	Uncertain	0.34
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.;.
Eigen	Benign	0.15
Eigen_PC	Benign	0.00068
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.97	.;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.6	L;.;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.8	D;D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		0.99	D;.;.
Vest4		0.50
MutPred		0.75		Loss of stability (P = 0.0079);.;Loss of stability (P = 0.0079);
MVP		0.84
MPC		0.053
ClinPred		0.95	D
GERP RS		3.1
Varity_R		0.069
gMVP		0.58

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: chr8-144800963;