Genetic Variant MST1R:p.Arg1391Gly (chr3-49887339-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002447.4(MST1R):c.4171C>G(p.Arg1391Gly) 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. 17/22 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. R1391W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

MST1R
NM_002447.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.50

Publications

1 publications found

Variant links:

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]

MST1R Gene-Disease associations (from GenCC):

nasopharyngeal carcinoma, susceptibility to, 3
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

MST1R links:

ENSG00000295244 (HGNC:):

ENSG00000295244 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23448747).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002447.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MST1R	NM_002447.4	MANE Select	c.4171C>G	p.Arg1391Gly	missense	Exon 20 of 20	NP_002438.2	Q04912-1
MST1R	NM_001244937.3		c.4024C>G	p.Arg1342Gly	missense	Exon 19 of 19	NP_001231866.1	Q04912-2
MST1R	NM_001437543.1		c.3964C>G	p.Arg1322Gly	missense	Exon 19 of 19	NP_001424472.1	H7C074

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MST1R	ENST00000296474.8	TSL:1 MANE Select	c.4171C>G	p.Arg1391Gly	missense	Exon 20 of 20	ENSP00000296474.3	Q04912-1
MST1R	ENST00000621387.4	TSL:1	c.3853C>G	p.Arg1285Gly	missense	Exon 18 of 18	ENSP00000482642.1	Q04912-7
MST1R	ENST00000858906.1		c.4174C>G	p.Arg1392Gly	missense	Exon 21 of 21	ENSP00000528965.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

0.0034

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.099

Eigen

Benign

-0.041

Eigen_PC

Benign

-0.079

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.76

M_CAP

Benign

0.045

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.35

MutationAssessor

Benign

1.8

PhyloP100

2.5

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.9

REVEL

Benign

0.15

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.72

Vest4

0.32

MutPred

0.23

Gain of relative solvent accessibility (P = 0.0249)

MVP

0.61

MPC

0.23

ClinPred

0.82

GERP RS

3.3

Varity_R

0.18

gMVP

0.44

Mutation Taster

=75/25

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over