3-49902693-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_002447.4(MST1R):c.917G>A(p.Arg306His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

MST1R
NM_002447.4 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 7.83

Publications

6 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:

ENSG00000230698 (HGNC:):

ENSG00000230698 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.927

BS2

High AC in GnomAdExome4 at 19 AD gene.

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.917G>A	p.Arg306His	missense	Exon 1 of 20	NP_002438.2	Q04912-1
MST1R	NM_001244937.3		c.917G>A	p.Arg306His	missense	Exon 1 of 19	NP_001231866.1	Q04912-2
MST1R	NM_001437543.1		c.917G>A	p.Arg306His	missense	Exon 1 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.917G>A	p.Arg306His	missense	Exon 1 of 20	ENSP00000296474.3	Q04912-1
MST1R	ENST00000621387.4	TSL:1	c.917G>A	p.Arg306His	missense	Exon 1 of 18	ENSP00000482642.1	Q04912-7
MST1R	ENST00000468525.5	TSL:1	n.917G>A		non_coding_transcript_exon	Exon 1 of 10

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000359

AC:

AN:

250828

AF XY:

0.0000516

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461116

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726866

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000202

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52676

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000989

AC:

AN:

1111994

Other (OTH)

AF:

0.00

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:risk factor

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Nasopharyngeal carcinoma, susceptibility to, 3 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

Eigen

Pathogenic

0.72

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.93

MetaSVM

Benign

-0.61

MutationAssessor

Pathogenic

3.2

PhyloP100

7.8

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-4.0

REVEL

Uncertain

0.57

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.66

MutPred

0.90

Gain of ubiquitination at K305 (P = 0.0397)

MVP

0.55

MPC

0.82

ClinPred

0.94

GERP RS

4.9

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.0

Varity_R

0.36

gMVP

0.67

Mutation Taster

=41/59

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over