Genetic Variant MST1R:p.Phe1299Ser (chr3-49889975-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002447.4(MST1R):c.3896T>C(p.Phe1299Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

MST1R
NM_002447.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.93

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 86 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MST1R	NM_002447.4 link	c.3896T>C	p.Phe1299Ser	missense_variant	Exon 19 of 20	ENST00000296474.8	NP_002438.2	Q04912-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MST1R	ENST00000296474.8 link	c.3896T>C	p.Phe1299Ser	missense_variant	Exon 19 of 20	1	NM_002447.4	ENSP00000296474.3		Q04912-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152104

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000319

AC:

AN:

251122

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000617

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000588

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.0000447

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000728

AC:

AN:

1111996

Other (OTH)

AF:

0.0000331

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.3896T>C (p.F1299S) alteration is located in exon 19 (coding exon 19) of the MST1R gene. This alteration results from a T to C substitution at nucleotide position 3896, causing the phenylalanine (F) at amino acid position 1299 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

Pathogenic

0.77

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

D;.;.;.

Eigen

Benign

-0.019

Eigen_PC

Benign

0.029

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.85

T;T;T;T

M_CAP

Benign

0.051

MetaRNN

Uncertain

0.73

D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;.;.;.

PhyloP100

2.9

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.8

D;.;.;D

REVEL

Uncertain

0.37

Sift

Uncertain

0.0020

D;.;.;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.69

MutPred

0.67

Gain of disorder (P = 0.0085);.;.;.;

MVP

0.49

MPC

0.98

ClinPred

0.89

GERP RS

1.9

Varity_R

0.60

gMVP

0.88

Mutation Taster

=51/49

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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chr3-49889975-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over