9-125438948-C-A

Position:

• chr9-125438948-C-A

Variant summary

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

The NM_001006617.3(MAPKAP1):​c.1508G>T​(p.Arg503Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAPKAP1 NM_001006617.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.42

Genes affected

MAPKAP1 (HGNC:18752): (MAPK associated protein 1) This gene encodes a protein that is highly similar to the yeast SIN1 protein, a stress-activated protein kinase. Alternatively spliced transcript variants encoding distinct isoforms have been described. Alternate polyadenylation sites as well as alternate 3' UTRs have been identified for transcripts of this gene. [provided by RefSeq, Jul 2008]

MAPKAP1 (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
MAPKAP1	NM_001006617.3	c.1508G>T	p.Arg503Ile	missense_variant	12/12	ENST00000265960.8	NP_001006618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPKAP1	ENST00000265960.8	c.1508G>T	p.Arg503Ile	missense_variant	12/12	1	NM_001006617.3	ENSP00000265960.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Jul 27, 2024

The c.1508G>T (p.R503I) alteration is located in exon 12 (coding exon 11) of the MAPKAP1 gene. This alteration results from a G to T substitution at nucleotide position 1508, causing the arginine (R) at amino acid position 503 to be replaced by an isoleucine (I). 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	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.90	.;D;.;.;D;.
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;.;D;.;D;D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.58	D;D;D;D;D;D
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.55	.;N;.;.;N;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.9	D;D;D;D;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0010	D;D;D;D;D;D
Sift4G	Uncertain	0.0090	D;D;D;D;D;D
Polyphen		1.0	D;D;D;.;D;.
Vest4		0.63
MutPred		0.46		.;Loss of disorder (P = 0.0244);.;.;Loss of disorder (P = 0.0244);.;
MVP		0.49
MPC		2.0
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.52
gMVP		0.66

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: chr9-128201227;