3-49684099-G-T

Variant names:

• chr3-49684099-G-T
• rs3197999
• NM_020998.4:c.2107C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020998.4(MST1):​c.2107C>A​(p.Arg703Ser) 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. 13/18 in silico tools predict a benign 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: 1.12

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]

APEH (HGNC:586): (acylaminoacyl-peptide hydrolase) This gene encodes the enzyme acylpeptide hydrolase, which catalyzes the hydrolysis of the terminal acetylated amino acid preferentially from small acetylated peptides. The acetyl amino acid formed by this hydrolase is further processed to acetate and a free amino acid by an aminoacylase. This gene is located within the same region of chromosome 3 (3p21) as the aminoacylase gene, and deletions at this locus are also associated with a decrease in aminoacylase activity. The acylpeptide hydrolase is a homotetrameric protein of 300 kDa with each subunit consisting of 732 amino acid residues. It can play an important role in destroying oxidatively damaged proteins in living cells. Deletions of this gene locus are found in various types of carcinomas, including small cell lung carcinoma and renal cell carcinoma. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13143897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MST1	NM_020998.4	c.2107C>A	p.Arg703Ser	missense_variant	Exon 18 of 18	ENST00000449682.3	NP_066278.3
APEH	NM_001640.4	c.*757G>T		downstream_gene_variant		ENST00000296456.10	NP_001631.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MST1	ENST00000449682.3	c.2107C>A	p.Arg703Ser	missense_variant	Exon 18 of 18	1	NM_020998.4	ENSP00000414287.2
APEH	ENST00000296456.10	c.*757G>T		downstream_gene_variant		1	NM_001640.4	ENSP00000296456.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	14
DANN	Benign	0.94
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.72	T
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.27
Sift	Benign	0.21	T
Sift4G	Benign	0.59	T
Polyphen		0.010	B
Vest4		0.30
MutPred		0.48		Loss of MoRF binding (P = 0.0236);
MVP		0.50
MPC		0.20
ClinPred		0.057	T
GERP RS		-2.8
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

Other links and lift over

dbSNP: rs3197999; hg19: chr3-49721532;