3-49684636-C-A

Variant names:

• chr3-49684636-C-A
• rs1013804856
• NM_020998.4:c.1790G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020998.4(MST1):​c.1790G>T​(p.Arg597Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MST1 NM_020998.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.39

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]

ENSG00000259970 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MST1	NM_020998.4	c.1790G>T	p.Arg597Leu	missense_variant	Exon 16 of 18	ENST00000449682.3	NP_066278.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MST1	ENST00000449682.3	c.1790G>T	p.Arg597Leu	missense_variant	Exon 16 of 18	1	NM_020998.4	ENSP00000414287.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Benign	0.039
Eigen_PC	Benign	0.058
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.079	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	-0.15	T
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.63
Sift	Benign	0.64	T
Sift4G	Benign	0.65	T
Polyphen		0.95	P
Vest4		0.72
MutPred		0.73		Loss of MoRF binding (P = 0.0679);
MVP		0.86
MPC		0.42
ClinPred		0.98	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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

Other links and lift over

dbSNP: rs1013804856; hg19: chr3-49722069;