11-130160143-C-T

Position:

• chr11-130160143-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000278742.6(ST14):​c.81+83C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 993,234 control chromosomes in the GnomAD database, including 1,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (251 hom., cov: 32)
  • Exomes 𝑓: 0.041 (884 hom.)
• Consequence: ST14 ENST00000278742.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00100

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 11-130160143-C-T is Benign according to our data. Variant chr11-130160143-C-T is described in ClinVar as [Benign]. Clinvar id is 1287856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST14	NM_021978.4	c.81+83C>T		intron_variant		ENST00000278742.6	NP_068813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST14	ENST00000278742.6	c.81+83C>T		intron_variant		1	NM_021978.4	ENSP00000278742	P1

Frequencies

GnomAD3 genomes AF: 0.0488 AC: 7422 AN: 152038 Hom.: 252 Cov.: 32

Gnomad AFR AF: 0.0678

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0323

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.0327

Gnomad MID AF: 0.0385

Gnomad NFE AF: 0.0375

Gnomad OTH AF: 0.0436

GnomAD4 exome AF: 0.0409 AC: 34385 AN: 841086 Hom.: 884 AF XY: 0.0405 AC XY: 16656 AN XY: 410864

Gnomad4 AFR exome AF: 0.0729

Gnomad4 AMR exome AF: 0.0291

Gnomad4 ASJ exome AF: 0.0296

Gnomad4 EAS exome AF: 0.131

Gnomad4 SAS exome AF: 0.0426

Gnomad4 FIN exome AF: 0.0326

Gnomad4 NFE exome AF: 0.0374

Gnomad4 OTH exome AF: 0.0449

GnomAD4 genome AF: 0.0488 AC: 7426 AN: 152148 Hom.: 251 Cov.: 32 AF XY: 0.0489 AC XY: 3634 AN XY: 74372

Gnomad4 AFR AF: 0.0679

Gnomad4 AMR AF: 0.0321

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.0404

Gnomad4 FIN AF: 0.0327

Gnomad4 NFE AF: 0.0375

Gnomad4 OTH AF: 0.0441

Alfa AF: 0.0401 Hom.: 136

Bravo AF: 0.0510

Asia WGS AF: 0.0860 AC: 298 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.5
DANN	Benign	0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3740883; hg19: chr11-130030038;