9-125506357-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001006617.3(MAPKAP1):c.1019C>G(p.Thr340Ser) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAPKAP1 NM_001006617.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.55

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, MAPKAP1
• BP4: Computational evidence support a benign effect (MetaRNN=0.21055955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPKAP1	NM_001006617.3	c.1019C>G	p.Thr340Ser	missense_variant	8/12	ENST00000265960.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPKAP1	ENST00000265960.8	c.1019C>G	p.Thr340Ser	missense_variant	8/12	1	NM_001006617.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Feb 28, 2024

The c.1019C>G (p.T340S) alteration is located in exon 8 (coding exon 7) of the MAPKAP1 gene. This alteration results from a C to G substitution at nucleotide position 1019, causing the threonine (T) at amino acid position 340 to be replaced by a serine (S). 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	0.11
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	22
Dann	Uncertain	0.98
Eigen	Benign	0.079
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T;.;.;T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.21	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.99	L;L;.;L;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.84	N;N;N;N;N
REVEL	Benign	0.056
Sift	Benign	0.55	T;T;T;T;T
Sift4G	Benign	0.46	T;T;T;T;T
Polyphen		0.047	B;B;.;B;.
Vest4		0.36
MutPred		0.44		Gain of disorder (P = 0.0242);Gain of disorder (P = 0.0242);.;Gain of disorder (P = 0.0242);.;
MVP		0.13
MPC		0.71
ClinPred		0.51	D
GERP RS		5.9
Varity_R		0.10
gMVP		0.34

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: chr9-128268636;