chr3-49685030-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020998.4(MST1):​c.1604G>A​(p.Arg535Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,609,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MST1
NM_020998.4 missense

Scores

4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3865946).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MST1NM_020998.4 linkc.1604G>A p.Arg535Gln missense_variant Exon 14 of 18 ENST00000449682.3 NP_066278.3 P26927G3XAK1Q53GN8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MST1ENST00000449682.3 linkc.1604G>A p.Arg535Gln missense_variant Exon 14 of 18 1 NM_020998.4 ENSP00000414287.2 G3XAK1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152042
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000232
AC:
5
AN:
215592
Hom.:
0
AF XY:
0.0000171
AC XY:
2
AN XY:
117284
show subpopulations
Gnomad AFR exome
AF:
0.0000821
Gnomad AMR exome
AF:
0.0000638
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000717
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000117
AC:
17
AN:
1457490
Hom.:
0
Cov.:
36
AF XY:
0.00000828
AC XY:
6
AN XY:
724968
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.0000449
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000465
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000721
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152042
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74262
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ExAC
AF:
0.0000249
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1604G>A (p.R535Q) alteration is located in exon 14 (coding exon 14) of the MST1 gene. This alteration results from a G to A substitution at nucleotide position 1604, causing the arginine (R) at amino acid position 535 to be replaced by a glutamine (Q). 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
-0.059
T
BayesDel_noAF
Benign
-0.13
CADD
Benign
21
DANN
Uncertain
1.0
Eigen
Benign
0.011
Eigen_PC
Benign
0.082
FATHMM_MKL
Benign
0.74
D
LIST_S2
Uncertain
0.86
D
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.39
T
MetaSVM
Uncertain
-0.22
T
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-1.0
N
REVEL
Uncertain
0.37
Sift
Benign
0.17
T
Sift4G
Benign
0.33
T
Polyphen
0.94
P
Vest4
0.34
MutPred
0.73
Gain of sheet (P = 0.1945);
MVP
0.86
MPC
0.20
ClinPred
0.077
T
GERP RS
2.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs767555694; hg19: chr3-49722463; API