3-49684742-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020998.4(MST1):​c.1765G>A​(p.Glu589Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000651 in 1,613,264 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

MST1
NM_020998.4 missense

Scores

7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.31
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MST1NM_020998.4 linkc.1765G>A p.Glu589Lys missense_variant Exon 15 of 18 ENST00000449682.3 NP_066278.3 P26927G3XAK1Q53GN8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MST1ENST00000449682.3 linkc.1765G>A p.Glu589Lys missense_variant Exon 15 of 18 1 NM_020998.4 ENSP00000414287.2 G3XAK1

Frequencies

GnomAD3 genomes
AF:
0.0000525
AC:
8
AN:
152248
Hom.:
0
Cov.:
33
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:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000240
AC:
6
AN:
250100
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135310
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000532
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000664
AC:
97
AN:
1461016
Hom.:
0
Cov.:
40
AF XY:
0.0000482
AC XY:
35
AN XY:
726830
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000792
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152248
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000602
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 13, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1765G>A (p.E589K) alteration is located in exon 15 (coding exon 15) of the MST1 gene. This alteration results from a G to A substitution at nucleotide position 1765, causing the glutamic acid (E) at amino acid position 589 to be replaced by a lysine (K). 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
BayesDel_addAF
Benign
-0.018
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
25
DANN
Uncertain
1.0
Eigen
Uncertain
0.20
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.031
D
MetaRNN
Uncertain
0.46
T
MetaSVM
Benign
-0.89
T
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-1.3
N
REVEL
Uncertain
0.52
Sift
Benign
0.18
T
Sift4G
Benign
0.58
T
Polyphen
0.89
P
Vest4
0.28
MutPred
0.54
Gain of MoRF binding (P = 0.002);
MVP
0.85
MPC
0.18
ClinPred
0.31
T
GERP RS
4.9
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs761248104; hg19: chr3-49722175; API