9-125585700-T-G

Position:

• chr9-125585700-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001006617.3(MAPKAP1):​c.526A>C​(p.Lys176Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAPKAP1 NM_001006617.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.94

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3874202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPKAP1	NM_001006617.3	c.526A>C	p.Lys176Gln	missense_variant	5/12	ENST00000265960.8	NP_001006618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPKAP1	ENST00000265960.8	c.526A>C	p.Lys176Gln	missense_variant	5/12	1	NM_001006617.3	ENSP00000265960.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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 16, 2024

The c.526A>C (p.K176Q) alteration is located in exon 5 (coding exon 4) of the MAPKAP1 gene. This alteration results from a A to C substitution at nucleotide position 526, causing the lysine (K) at amino acid position 176 to be replaced by a glutamine (Q). 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	0.13
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.56	.;D;.;D;.;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D;.;D;D;D;D
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.39	T;T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.9	L;L;L;L;L;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.8	N;N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.036	D;D;T;D;D;D
Sift4G	Uncertain	0.048	D;T;T;T;T;.
Polyphen		0.038	B;B;P;B;B;.
Vest4		0.68
MutPred		0.55		Loss of ubiquitination at K176 (P = 0.0244);Loss of ubiquitination at K176 (P = 0.0244);Loss of ubiquitination at K176 (P = 0.0244);Loss of ubiquitination at K176 (P = 0.0244);Loss of ubiquitination at K176 (P = 0.0244);.;
MVP		0.39
MPC		1.1
ClinPred		0.80	D
GERP RS		5.7
Varity_R		0.34
gMVP		0.68

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: chr9-128347979;