9-125438948-C-A

Variant names:

• chr9-125438948-C-A
• NM_001006617.3:c.1508G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006617.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAP1	NM_001006617.3	MANE Select	c.1508G>T	p.Arg503Ile	missense	Exon 12 of 12	NP_001006618.1	Q9BPZ7-1
	MAPKAP1	NM_024117.4		c.1400G>T	p.Arg467Ile	missense	Exon 11 of 11	NP_077022.1	Q9BPZ7-2
	MAPKAP1	NM_001006619.2		c.1367G>T	p.Arg456Ile	missense	Exon 11 of 11	NP_001006620.1	Q9BPZ7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAP1	ENST00000265960.8	TSL:1 MANE Select	c.1508G>T	p.Arg503Ile	missense	Exon 12 of 12	ENSP00000265960.3	Q9BPZ7-1
	MAPKAP1	ENST00000350766.7	TSL:1	c.1400G>T	p.Arg467Ile	missense	Exon 11 of 11	ENSP00000265961.5	Q9BPZ7-2
	MAPKAP1	ENST00000373511.6	TSL:1	c.1367G>T	p.Arg456Ile	missense	Exon 11 of 11	ENSP00000362610.2	Q9BPZ7-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.55	N
PhyloP100		5.4
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.46		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
Mutation Taster		=14/86	disease causing

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

Other links and lift over

hg19: chr9-128201227;