Variant chr3-49890005-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_002447.4(MST1R):c.3866G>A(p.Arg1289His) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

MST1R
NM_002447.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19317055).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MST1R	NM_002447.4 linkuse as main transcript	c.3866G>A	p.Arg1289His	missense_variant	19/20	ENST00000296474.8	NP_002438.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MST1R	ENST00000296474.8 linkuse as main transcript	c.3866G>A	p.Arg1289His	missense_variant	19/20	1	NM_002447.4	ENSP00000296474	P2	Q04912-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250534

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135424

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:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461442

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727022

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

The c.3866G>A (p.R1289H) alteration is located in exon 19 (coding exon 19) of the MST1R gene. This alteration results from a G to A substitution at nucleotide position 3866, causing the arginine (R) at amino acid position 1289 to be replaced by a histidine (H). 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

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

0.0046

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;.;.;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.39

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

T;D;T;D

M_CAP

Benign

0.078

MetaRNN

Benign

0.19

T;T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.50

N;.;.;.

MutationTaster

Benign

0.91

N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.24

N;.;.;N

REVEL

Benign

0.27

Sift

Uncertain

0.0020

D;.;.;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

0.053

B;.;.;.

Vest4

0.23

MVP

0.41

MPC

0.23

ClinPred

0.74

GERP RS

4.0

Varity_R

0.25

gMVP

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over