chr11-130160143-C-T

Variant names:

• chr11-130160143-C-T
• rs3740883
• NM_021978.4:c.81+83C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021978.4(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 NM_021978.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00100
• Publications: 1 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.81+83C>T		intron	N/A	NP_068813.1	Q9Y5Y6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST14	ENST00000278742.6	TSL:1 MANE Select	c.81+83C>T		intron	N/A	ENSP00000278742.5	Q9Y5Y6
	ST14	ENST00000894129.1		c.81+83C>T		intron	N/A	ENSP00000564188.1
	ST14	ENST00000894128.1		c.81+83C>T		intron	N/A	ENSP00000564187.1

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

African (AFR) AF: 0.0729 AC: 1226 AN: 16824

American (AMR) AF: 0.0291 AC: 226 AN: 7770

Ashkenazi Jewish (ASJ) AF: 0.0296 AC: 365 AN: 12322

East Asian (EAS) AF: 0.131 AC: 3162 AN: 24184

South Asian (SAS) AF: 0.0426 AC: 1233 AN: 28976

European-Finnish (FIN) AF: 0.0326 AC: 1149 AN: 35246

Middle Eastern (MID) AF: 0.0469 AC: 114 AN: 2430

European-Non Finnish (NFE) AF: 0.0374 AC: 25354 AN: 678704

Other (OTH) AF: 0.0449 AC: 1556 AN: 34630

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

African (AFR) AF: 0.0679 AC: 2821 AN: 41542

American (AMR) AF: 0.0321 AC: 491 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3472

East Asian (EAS) AF: 0.151 AC: 771 AN: 5110

South Asian (SAS) AF: 0.0404 AC: 195 AN: 4830

European-Finnish (FIN) AF: 0.0327 AC: 347 AN: 10608

Middle Eastern (MID) AF: 0.0377 AC: 11 AN: 292

European-Non Finnish (NFE) AF: 0.0375 AC: 2552 AN: 67980

Other (OTH) AF: 0.0441 AC: 93 AN: 2110

Alfa AF: 0.0414 Hom.: 231

Bravo AF: 0.0510

Asia WGS AF: 0.0860 AC: 298 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.5
DANN	Benign	0.94
PhyloP100		0.0010
PromoterAI		-0.10	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3740883; hg19: chr11-130030038;