Genetic Variant NM_002447.4:c.3845C>G (chr3-49890026-G-C) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_002447.4(MST1R):c.3845C>G(p.Thr1282Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. T1282K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

MST1R
NM_002447.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.99

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.971

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.3845C>G	p.Thr1282Arg	missense	Exon 19 of 20	NP_002438.2	Q04912-1
MST1R	NM_001244937.3		c.3698C>G	p.Thr1233Arg	missense	Exon 18 of 19	NP_001231866.1	Q04912-2
MST1R	NM_001437543.1		c.3638C>G	p.Thr1213Arg	missense	Exon 18 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.3845C>G	p.Thr1282Arg	missense	Exon 19 of 20	ENSP00000296474.3	Q04912-1
MST1R	ENST00000621387.4	TSL:1	c.3527C>G	p.Thr1176Arg	missense	Exon 17 of 18	ENSP00000482642.1	Q04912-7
MST1R	ENST00000858906.1		c.3848C>G	p.Thr1283Arg	missense	Exon 20 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

Pathogenic

0.87

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.60

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

1.0

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.97

MetaSVM

Uncertain

-0.0086

MutationAssessor

Pathogenic

3.0

PhyloP100

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-5.4

REVEL

Pathogenic

0.75

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.92

MutPred

0.89

Gain of solvent accessibility (P = 0.0584)

MVP

0.69

MPC

0.79

ClinPred

1.0

GERP RS

5.8

Varity_R

0.97

gMVP

0.97

Mutation Taster

=17/83

disease causing

(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