chr3-49887339-G-C

Variant names:

• chr3-49887339-G-C
• rs533872004
• NM_002447.4:c.4171C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002447.4(MST1R):​c.4171C>G​(p.Arg1391Gly) 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 benign outcome for this variant. 17/22 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. R1391W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MST1R NM_002447.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50
• Publications: 1 publications found

Genes affected

MST1R (HGNC:7381): (macrophage stimulating 1 receptor) This gene encodes a cell surface receptor for macrophage-stimulating protein (MSP) with tyrosine kinase activity. The mature form of this protein is a heterodimer of disulfide-linked alpha and beta subunits, generated by proteolytic cleavage of a single-chain precursor. The beta subunit undergoes tyrosine phosphorylation upon stimulation by MSP. This protein is expressed on the ciliated epithelia of the mucociliary transport apparatus of the lung, and together with MSP, thought to be involved in host defense. Alternative splicing generates multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Jan 2016]

MST1R Gene-Disease associations (from GenCC):

• nasopharyngeal carcinoma, susceptibility to, 3

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000295244 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23448747).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MST1R	NM_002447.4	c.4171C>G	p.Arg1391Gly	missense_variant	Exon 20 of 20	ENST00000296474.8	NP_002438.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MST1R	ENST00000296474.8	c.4171C>G	p.Arg1391Gly	missense_variant	Exon 20 of 20	1	NM_002447.4	ENSP00000296474.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	0.0034	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.099	T;.;.;.;.
Eigen	Benign	-0.041
Eigen_PC	Benign	-0.079
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.76	T;T;T;T;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.23	T;T;T;T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.8	L;.;.;.;.
PhyloP100		2.5
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.9	N;.;.;.;N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D;.;.;.;D
Sift4G	Pathogenic	0.0	D;T;D;D;D
Polyphen		0.72	P;.;.;.;.
Vest4		0.32
MutPred		0.23		Gain of relative solvent accessibility (P = 0.0249);.;.;.;.;
MVP		0.61
MPC		0.23
ClinPred		0.82	D
GERP RS		3.3
Varity_R		0.18
gMVP		0.44
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs533872004; hg19: chr3-49924772;