Variant 11-130188542-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021978.4(ST14):c.254G>A(p.Arg85His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 1,614,070 control chromosomes in the GnomAD database, including 1,982 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 227 hom., cov: 33)

Exomes 𝑓: 0.043 ( 1755 hom. )

Consequence

ST14
NM_021978.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.999

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016971529).

BP6

Variant 11-130188542-G-A is Benign according to our data. Variant chr11-130188542-G-A is described in ClinVar as [Benign]. Clinvar id is 1625929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST14	NM_021978.4 linkuse as main transcript	c.254G>A	p.Arg85His	missense_variant	3/19	ENST00000278742.6	NP_068813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST14	ENST00000278742.6 linkuse as main transcript	c.254G>A	p.Arg85His	missense_variant	3/19	1	NM_021978.4	ENSP00000278742	P1

Frequencies

GnomAD3 genomes

AF:

0.0386

AC:

5876

AN:

152192

Hom.:

228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00815

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.0181

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0288

Gnomad FIN

AF:

0.0760

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0387

Gnomad OTH

AF:

0.0407

GnomAD3 exomes

AF:

0.0537

AC:

13494

AN:

251338

Hom.:

671

AF XY:

0.0509

AC XY:

6913

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.00689

Gnomad AMR exome

AF:

0.153

Gnomad ASJ exome

AF:

0.0197

Gnomad EAS exome

AF:

0.000653

Gnomad SAS exome

AF:

0.0358

Gnomad FIN exome

AF:

0.0814

Gnomad NFE exome

AF:

0.0416

Gnomad OTH exome

AF:

0.0493

GnomAD4 exome

AF:

0.0425

AC:

62157

AN:

1461760

Hom.:

1755

Cov.:

AF XY:

0.0420

AC XY:

30572

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.00559

Gnomad4 AMR exome

AF:

0.151

Gnomad4 ASJ exome

AF:

0.0196

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.0372

Gnomad4 FIN exome

AF:

0.0792

Gnomad4 NFE exome

AF:

0.0404

Gnomad4 OTH exome

AF:

0.0366

GnomAD4 genome

AF:

0.0386

AC:

5876

AN:

152310

Hom.:

227

Cov.:

AF XY:

0.0412

AC XY:

3071

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00813

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.0181

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0280

Gnomad4 FIN

AF:

0.0760

Gnomad4 NFE

AF:

0.0387

Gnomad4 OTH

AF:

0.0393

Alfa

AF:

0.0352

Hom.:

181

Bravo

AF:

0.0408

TwinsUK

AF:

0.0448

AC:

166

ALSPAC

AF:

0.0392

AC:

151

ESP6500AA

AF:

0.00772

AC:

ESP6500EA

AF:

0.0375

AC:

322

ExAC

AF:

0.0493

AC:

5979

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.96

REVEL

Uncertain

0.29

Sift

Benign

0.052

Sift4G

Uncertain

0.036

Polyphen

1.0

Vest4

0.10

MPC

1.2

ClinPred

0.024

GERP RS

0.52

Varity_R

0.063

gMVP

0.30

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