11-130160029-G-T

Position:

• chr11-130160029-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021978.4(ST14):​c.50G>T​(p.Gly17Val) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G17A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ST14 NM_021978.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.03

Genes affected

ST14 (HGNC:11344): (ST14 transmembrane serine protease matriptase) The protein encoded by this gene is an epithelial-derived, integral membrane serine protease. This protease forms a complex with the Kunitz-type serine protease inhibitor, HAI-1, and is found to be activated by sphingosine 1-phosphate. This protease has been shown to cleave and activate hepatocyte growth factor/scattering factor, and urokinase plasminogen activator, which suggest the function of this protease as an epithelial membrane activator for other proteases and latent growth factors. The expression of this protease has been associated with breast, colon, prostate, and ovarian tumors, which implicates its role in cancer invasion, and metastasis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27173364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST14	NM_021978.4	c.50G>T	p.Gly17Val	missense_variant	1/19	ENST00000278742.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST14	ENST00000278742.6	c.50G>T	p.Gly17Val	missense_variant	1/19	1	NM_021978.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1283572 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 631368

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.50G>T (p.G17V) alteration is located in exon 1 (coding exon 1) of the ST14 gene. This alteration results from a G to T substitution at nucleotide position 50, causing the glycine (G) at amino acid position 17 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.034
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.88	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Benign	0.81	L
MutationTaster	Benign	0.90	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.81	N
REVEL	Uncertain	0.39
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.29
MutPred		0.31		Loss of catalytic residue at G17 (P = 0.0171);
MVP		0.61
MPC		0.71
ClinPred		0.47	T
GERP RS		1.6
Varity_R		0.19
gMVP		0.23

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: rs1479825864; hg19: chr11-130029924;