Variant 3-49898669-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002447.4(MST1R):c.1568A>G(p.Gln523Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 1,613,800 control chromosomes in the GnomAD database, including 192,949 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.51 ( 20913 hom., cov: 34)

Exomes 𝑓: 0.47 ( 172036 hom. )

Consequence

MST1R
NM_002447.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.968

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.325076E-6).

BP6

Variant 3-49898669-T-C is Benign according to our data. Variant chr3-49898669-T-C is described in ClinVar as [Benign]. Clinvar id is 1237612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MST1R	NM_002447.4 link	c.1568A>G	p.Gln523Arg	missense_variant	4/20	ENST00000296474.8	NP_002438.2	Q04912-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MST1R	ENST00000296474.8 link	c.1568A>G	p.Gln523Arg	missense_variant	4/20	1	NM_002447.4	ENSP00000296474.3		Q04912-1

Frequencies

GnomAD3 genomes

AF:

0.506

AC:

76985

AN:

152036

Hom.:

20883

Cov.:

show subpopulations

Gnomad AFR

AF:

0.670

Gnomad AMI

AF:

0.537

Gnomad AMR

AF:

0.398

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.502

Gnomad OTH

AF:

0.501

GnomAD3 exomes

AF:

0.408

AC:

102273

AN:

250958

Hom.:

23417

AF XY:

0.404

AC XY:

54858

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.677

Gnomad AMR exome

AF:

0.289

Gnomad ASJ exome

AF:

0.402

Gnomad EAS exome

AF:

0.146

Gnomad SAS exome

AF:

0.233

Gnomad FIN exome

AF:

0.389

Gnomad NFE exome

AF:

0.497

Gnomad OTH exome

AF:

0.441

GnomAD4 exome

AF:

0.475

AC:

693707

AN:

1461646

Hom.:

172036

Cov.:

AF XY:

0.468

AC XY:

340478

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.676

Gnomad4 AMR exome

AF:

0.303

Gnomad4 ASJ exome

AF:

0.405

Gnomad4 EAS exome

AF:

0.153

Gnomad4 SAS exome

AF:

0.241

Gnomad4 FIN exome

AF:

0.390

Gnomad4 NFE exome

AF:

0.511

Gnomad4 OTH exome

AF:

0.467

GnomAD4 genome

AF:

0.506

AC:

77063

AN:

152154

Hom.:

20913

Cov.:

AF XY:

0.491

AC XY:

36564

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.670

Gnomad4 AMR

AF:

0.398

Gnomad4 ASJ

AF:

0.394

Gnomad4 EAS

AF:

0.143

Gnomad4 SAS

AF:

0.234

Gnomad4 FIN

AF:

0.384

Gnomad4 NFE

AF:

0.502

Gnomad4 OTH

AF:

0.504

Alfa

AF:

0.488

Hom.:

36075

Bravo

AF:

0.521

TwinsUK

AF:

0.517

AC:

1916

ALSPAC

AF:

0.520

AC:

2003

ESP6500AA

AF:

0.667

AC:

2941

ESP6500EA

AF:

0.506

AC:

4350

ExAC

AF:

0.417

AC:

50578

Asia WGS

AF:

0.290

AC:

1010

AN:

3478

EpiCase

AF:

0.498

EpiControl

AF:

0.497

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 23, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

MST1R-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0050

DANN

Benign

0.45

DEOGEN2

Benign

0.066

T;.;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.060

T;T;T

MetaRNN

Benign

0.0000023

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.13

N;.;N

PrimateAI

Benign

0.19

PROVEAN

Benign

0.48

N;.;N

REVEL

Benign

0.026

Sift

Benign

1.0

T;.;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.019

MPC

0.20

ClinPred

0.0063

GERP RS

-6.8

Varity_R

0.037

gMVP

0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over