rs2230590

chr3-49898669-T-Achr3-49898669-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002447.4(MST1R):c.1568A>T(p.Gln523Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q523R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: MST1R NM_002447.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.968

Genes affected

MST1R (HGNC:7381): (macrophage stimulating 1 receptor) This gene encodes a cell surface receptor for macrophage-stimulating protein (MSP) with tyrosine kinase activity. The mature form of this protein is a heterodimer of disulfide-linked alpha and beta subunits, generated by proteolytic cleavage of a single-chain precursor. The beta subunit undergoes tyrosine phosphorylation upon stimulation by MSP. This protein is expressed on the ciliated epithelia of the mucociliary transport apparatus of the lung, and together with MSP, thought to be involved in host defense. Alternative splicing generates multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10324165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MST1R	NM_002447.4	c.1568A>T	p.Gln523Leu	missense_variant	4/20	ENST00000296474.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MST1R	ENST00000296474.8	c.1568A>T	p.Gln523Leu	missense_variant	4/20	1	NM_002447.4	P2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 65

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	0.056
Dann	Benign	0.61
DEOGEN2	Benign	0.15	T;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.42	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;L
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.5	N;.;N
REVEL	Benign	0.026
Sift	Benign	0.17	T;.;T
Sift4G	Benign	0.25	T;T;T
Polyphen		0.039	B;.;.
Vest4		0.24
MutPred		0.37		Gain of sheet (P = 0.1208);.;Gain of sheet (P = 0.1208);
MVP		0.15
MPC		0.19
ClinPred		0.19	T
GERP RS		-6.8
Varity_R		0.086
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2230590; hg19: chr3-49936102;