Variant 3-49684379-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_020998.4(MST1):c.1951C>T(p.Arg651*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,613,284 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0085 ( 10 hom., cov: 33)

Exomes 𝑓: 0.014 ( 167 hom. )

Consequence

MST1
NM_020998.4 stop_gained

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.56

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.014 (20457/1460974) while in subpopulation MID AF= 0.021 (121/5762). AF 95% confidence interval is 0.018. There are 167 homozygotes in gnomad4_exome. There are 10384 alleles in male gnomad4_exome subpopulation. Median coverage is 40. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MST1	NM_020998.4 link	c.1951C>T	p.Arg651*	stop_gained	Exon 17 of 18	ENST00000449682.3	NP_066278.3	P26927G3XAK1Q53GN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MST1	ENST00000449682.3 link	c.1951C>T	p.Arg651*	stop_gained	Exon 17 of 18	1	NM_020998.4	ENSP00000414287.2		G3XAK1

Frequencies

GnomAD3 genomes

AF:

0.00852

AC:

1296

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.00537

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0136

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.0111

AC:

2786

AN:

250790

Hom.:

AF XY:

0.0114

AC XY:

1546

AN XY:

135604

show subpopulations

Gnomad AFR exome

AF:

0.00234

Gnomad AMR exome

AF:

0.00546

Gnomad ASJ exome

AF:

0.0211

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0102

Gnomad FIN exome

AF:

0.00564

Gnomad NFE exome

AF:

0.0161

Gnomad OTH exome

AF:

0.0139

GnomAD4 exome

AF:

0.0140

AC:

20457

AN:

1460974

Hom.:

167

Cov.:

AF XY:

0.0143

AC XY:

10384

AN XY:

726800

show subpopulations

Gnomad4 AFR exome

AF:

0.00224

Gnomad4 AMR exome

AF:

0.00543

Gnomad4 ASJ exome

AF:

0.0225

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.00554

Gnomad4 NFE exome

AF:

0.0157

Gnomad4 OTH exome

AF:

0.0135

GnomAD4 genome

AF:

0.00850

AC:

1295

AN:

152310

Hom.:

Cov.:

AF XY:

0.00781

AC XY:

582

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00193

Gnomad4 AMR

AF:

0.00627

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0114

Gnomad4 FIN

AF:

0.00537

Gnomad4 NFE

AF:

0.0136

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.0142

Hom.:

Bravo

AF:

0.00841

TwinsUK

AF:

0.0162

AC:

ALSPAC

AF:

0.0171

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.0134

AC:

115

ExAC

AF:

0.0113

AC:

1373

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0126

EpiControl

AF:

0.0135

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MST1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.54

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.93

Vest4

0.93

ClinPred

0.075

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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