3-49684430-T-G

Variant names:

• chr3-49684430-T-G
• NM_020998.4:c.1900A>C

Variant summary

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

The NM_020998.4(MST1):​c.1900A>C​(p.Asn634His) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,148 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: MST1 NM_020998.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.55
• Publications: 0 publications found

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]

MST1 Gene-Disease associations (from GenCC):

• combined immunodeficiency due to STK4 deficiency

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• epidermodysplasia verruciformis

  Inheritance: Unknown Classification: MODERATE Submitted by: Genomics England PanelApp

ENSG00000259970 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020998.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MST1	NM_020998.4	MANE Select	c.1900A>C	p.Asn634His	missense	Exon 17 of 18	NP_066278.3
	MST1	NM_001393581.1		c.1936A>C	p.Asn646His	missense	Exon 17 of 18	NP_001380510.1
	MST1	NM_001393582.1		c.1900A>C	p.Asn634His	missense	Exon 17 of 18	NP_001380511.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MST1	ENST00000449682.3	TSL:1 MANE Select	c.1900A>C	p.Asn634His	missense	Exon 17 of 18	ENSP00000414287.2	G3XAK1
	MST1	ENST00000448220.5	TSL:5	c.307A>C	p.Asn103His	missense	Exon 4 of 5	ENSP00000394756.1	H7C0F8
	MST1	ENST00000479115.5	TSL:5	n.1955A>C		non_coding_transcript_exon	Exon 5 of 6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461148 Hom.: 0 Cov.: 41 AF XY: 0.00000825 AC XY: 6 AN XY: 726872

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111834

Other (OTH) AF: 0.0000331 AC: 2 AN: 60370

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Uncertain	0.98
Eigen	Benign	-0.040
Eigen_PC	Benign	-0.034
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Uncertain	0.075	D
PhyloP100		5.6
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.46
Sift	Benign	0.16	T
Sift4G	Benign	0.099	T
Polyphen		0.95	P
Vest4		0.34
MutPred		0.66		Gain of disorder (P = 0.13)
MVP		0.84
MPC		0.26
ClinPred		0.65	D
GERP RS		4.3
gMVP		0.77
Mutation Taster		=78/22	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

hg19: chr3-49721863;