Variant rs3197999 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020998.4(MST1):c.2107C>T(p.Arg703Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 1,612,770 control chromosomes in the GnomAD database, including 65,085 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 5799 hom., cov: 33)

Exomes 𝑓: 0.28 ( 59286 hom. )

Consequence

MST1
NM_020998.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.12

Variant links:

Genes affected

MST1 (HGNC:7380): (macrophage stimulating 1) The protein encoded by this gene contains four kringle domains and a serine protease domain, similar to that found in hepatic growth factor. Despite the presence of the serine protease domain, the encoded protein may not have any proteolytic activity. The receptor for this protein is RON tyrosine kinase, which upon activation stimulates ciliary motility of ciliated epithelial lung cells. This protein is secreted and cleaved to form an alpha chain and a beta chain bridged by disulfide bonds. [provided by RefSeq, Jan 2010]

MST1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004493147).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MST1	NM_020998.4 linkuse as main transcript	c.2107C>T	p.Arg703Cys	missense_variant	18/18	ENST00000449682.3	NP_066278.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MST1	ENST00000449682.3 linkuse as main transcript	c.2107C>T	p.Arg703Cys	missense_variant	18/18	1	NM_020998.4	ENSP00000414287	P1

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40118

AN:

152004

Hom.:

5798

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.203

Gnomad ASJ

AF:

0.443

Gnomad EAS

AF:

0.0451

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.284

Gnomad OTH

AF:

0.280

GnomAD3 exomes

AF:

0.257

AC:

64425

AN:

250726

Hom.:

9703

AF XY:

0.260

AC XY:

35281

AN XY:

135544

show subpopulations

Gnomad AFR exome

AF:

0.230

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.440

Gnomad EAS exome

AF:

0.0453

Gnomad SAS exome

AF:

0.220

Gnomad FIN exome

AF:

0.418

Gnomad NFE exome

AF:

0.291

Gnomad OTH exome

AF:

0.283

GnomAD4 exome

AF:

0.277

AC:

405087

AN:

1460650

Hom.:

59286

Cov.:

AF XY:

0.276

AC XY:

200855

AN XY:

726644

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.151

Gnomad4 ASJ exome

AF:

0.439

Gnomad4 EAS exome

AF:

0.0436

Gnomad4 SAS exome

AF:

0.227

Gnomad4 FIN exome

AF:

0.409

Gnomad4 NFE exome

AF:

0.286

Gnomad4 OTH exome

AF:

0.281

GnomAD4 genome

AF:

0.264

AC:

40134

AN:

152120

Hom.:

5799

Cov.:

AF XY:

0.266

AC XY:

19756

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.231

Gnomad4 AMR

AF:

0.202

Gnomad4 ASJ

AF:

0.443

Gnomad4 EAS

AF:

0.0452

Gnomad4 SAS

AF:

0.209

Gnomad4 FIN

AF:

0.424

Gnomad4 NFE

AF:

0.284

Gnomad4 OTH

AF:

0.278

Alfa

AF:

0.280

Hom.:

12624

Bravo

AF:

0.245

TwinsUK

AF:

0.297

AC:

1101

ALSPAC

AF:

0.279

AC:

1075

ESP6500AA

AF:

0.235

AC:

1036

ESP6500EA

AF:

0.294

AC:

2525

ExAC

AF:

0.255

AC:

30977

Asia WGS

AF:

0.128

AC:

451

AN:

3478

EpiCase

AF:

0.294

EpiControl

AF:

0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.52

Sift

Uncertain

0.020

Sift4G

Uncertain

0.045

Polyphen

0.73

Vest4

0.35

MPC

0.46

ClinPred

0.025

GERP RS

-2.8

gMVP

0.76

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over