Genetic Variant ST14:p.Gly17Val (chr11-130160029-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.03

Publications

0 publications found

Variant links:

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]

ST14 Gene-Disease associations (from GenCC):

autosomal recessive congenital ichthyosis 11
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ST14 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27173364).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021978.4. 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
	ST14	NM_021978.4	MANE Select	c.50G>T	p.Gly17Val	missense	Exon 1 of 19	NP_068813.1	Q9Y5Y6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ST14	ENST00000278742.6	TSL:1 MANE Select	c.50G>T	p.Gly17Val	missense	Exon 1 of 19	ENSP00000278742.5	Q9Y5Y6
ST14	ENST00000894129.1		c.50G>T	p.Gly17Val	missense	Exon 1 of 19	ENSP00000564188.1
ST14	ENST00000894128.1		c.50G>T	p.Gly17Val	missense	Exon 1 of 19	ENSP00000564187.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1283572

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

631368

African (AFR)

AF:

0.00

AC:

AN:

26012

American (AMR)

AF:

0.00

AC:

AN:

22784

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21784

East Asian (EAS)

AF:

0.00

AC:

AN:

27480

South Asian (SAS)

AF:

0.00

AC:

AN:

65110

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4350

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1018690

Other (OTH)

AF:

0.00

AC:

AN:

51948

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.075

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

Eigen

Benign

-0.034

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.88

MetaRNN

Benign

0.27

MetaSVM

Uncertain

-0.10

MutationAssessor

Benign

0.81

PhyloP100

2.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.81

REVEL

Uncertain

0.39

Sift

Uncertain

0.010

Sift4G

Uncertain

0.020

Polyphen

1.0

Vest4

0.29

MutPred

0.31

Loss of catalytic residue at G17 (P = 0.0171)

MVP

0.61

MPC

0.71

ClinPred

0.47

GERP RS

1.6

PromoterAI

0.070

Neutral

(source)

Varity_R

0.19

gMVP

0.23

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over