3-49684099-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R703H) has been classified as Uncertain significance.

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

Publications

205 publications found

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:

APEH (HGNC:586): (acylaminoacyl-peptide hydrolase) This gene encodes the enzyme acylpeptide hydrolase, which catalyzes the hydrolysis of the terminal acetylated amino acid preferentially from small acetylated peptides. The acetyl amino acid formed by this hydrolase is further processed to acetate and a free amino acid by an aminoacylase. This gene is located within the same region of chromosome 3 (3p21) as the aminoacylase gene, and deletions at this locus are also associated with a decrease in aminoacylase activity. The acylpeptide hydrolase is a homotetrameric protein of 300 kDa with each subunit consisting of 732 amino acid residues. It can play an important role in destroying oxidatively damaged proteins in living cells. Deletions of this gene locus are found in various types of carcinomas, including small cell lung carcinoma and renal cell carcinoma. [provided by RefSeq, Jul 2008]

APEH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020998.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MST1	NM_020998.4	MANE Select	c.2107C>T	p.Arg703Cys	missense	Exon 18 of 18	NP_066278.3
MST1	NM_001393581.1		c.2143C>T	p.Arg715Cys	missense	Exon 18 of 18	NP_001380510.1
MST1	NM_001393582.1		c.2050C>T	p.Arg684Cys	missense	Exon 18 of 18	NP_001380511.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MST1	ENST00000449682.3	TSL:1 MANE Select	c.2107C>T	p.Arg703Cys	missense	Exon 18 of 18	ENSP00000414287.2
MST1	ENST00000448220.5	TSL:5	c.514C>T	p.Arg172Cys	missense	Exon 5 of 5	ENSP00000394756.1
MST1	ENST00000479115.5	TSL:5	n.2162C>T		non_coding_transcript_exon	Exon 6 of 6

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

GnomAD2 exomes

AF:

0.257

AC:

64425

AN:

250726

AF XY:

0.260

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 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

African (AFR)

AF:

0.233

AC:

7805

AN:

33468

American (AMR)

AF:

0.151

AC:

6740

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

11459

AN:

26092

East Asian (EAS)

AF:

0.0436

AC:

1730

AN:

39658

South Asian (SAS)

AF:

0.227

AC:

19557

AN:

86228

European-Finnish (FIN)

AF:

0.409

AC:

21739

AN:

53112

Middle Eastern (MID)

AF:

0.299

AC:

1723

AN:

5758

European-Non Finnish (NFE)

AF:

0.286

AC:

317391

AN:

1111292

Other (OTH)

AF:

0.281

AC:

16943

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

19467

38934

58402

77869

97336

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10370

20740

31110

41480

51850

<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:

0.264

AC:

40134

AN:

152120

Hom.:

5799

Cov.:

AF XY:

0.266

AC XY:

19756

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.231

AC:

9608

AN:

41504

American (AMR)

AF:

0.202

AC:

3096

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.443

AC:

1536

AN:

3470

East Asian (EAS)

AF:

0.0452

AC:

234

AN:

5176

South Asian (SAS)

AF:

0.209

AC:

1010

AN:

4822

European-Finnish (FIN)

AF:

0.424

AC:

4475

AN:

10562

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.284

AC:

19319

AN:

67966

Other (OTH)

AF:

0.278

AC:

587

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1502

3004

4507

6009

7511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.275

Hom.:

24848

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

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

PhyloP100

1.1

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

Mutation Taster

=96/4

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over