11-130210122-C-T

Variant names:

• chr11-130210122-C-T
• rs704624
• NM_021978.4:c.*299C>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.*299C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 393,528 control chromosomes in the GnomAD database, including 69,597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24066 hom., cov: 33)
  • Exomes 𝑓: 0.61 (45531 hom.)
• Consequence: ST14 NM_021978.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.04
• Publications: 11 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-130210122-C-T is Benign according to our data. Variant chr11-130210122-C-T is described in ClinVar as Benign. ClinVar VariationId is 1262519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.693 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.*299C>T		3_prime_UTR	Exon 19 of 19	NP_068813.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST14	ENST00000278742.6	TSL:1 MANE Select	c.*299C>T		3_prime_UTR	Exon 19 of 19	ENSP00000278742.5
	ST14	ENST00000894129.1		c.*299C>T		3_prime_UTR	Exon 19 of 19	ENSP00000564188.1
	ST14	ENST00000894128.1		c.*299C>T		3_prime_UTR	Exon 19 of 19	ENSP00000564187.1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84878 AN: 151930 Hom.: 24056 Cov.: 33

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.563

GnomAD4 exome AF: 0.612 AC: 147671 AN: 241480 Hom.: 45531 Cov.: 2 AF XY: 0.619 AC XY: 78118 AN XY: 126210

African (AFR) AF: 0.480 AC: 3737 AN: 7790

American (AMR) AF: 0.549 AC: 5536 AN: 10088

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 4367 AN: 7382

East Asian (EAS) AF: 0.546 AC: 7614 AN: 13944

South Asian (SAS) AF: 0.710 AC: 21436 AN: 30212

European-Finnish (FIN) AF: 0.670 AC: 8315 AN: 12412

Middle Eastern (MID) AF: 0.631 AC: 681 AN: 1080

European-Non Finnish (NFE) AF: 0.605 AC: 87672 AN: 144874

Other (OTH) AF: 0.607 AC: 8313 AN: 13698

GnomAD4 genome AF: 0.558 AC: 84915 AN: 152048 Hom.: 24066 Cov.: 33 AF XY: 0.565 AC XY: 41970 AN XY: 74304

African (AFR) AF: 0.470 AC: 19468 AN: 41464

American (AMR) AF: 0.540 AC: 8249 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2035 AN: 3472

East Asian (EAS) AF: 0.505 AC: 2598 AN: 5140

South Asian (SAS) AF: 0.713 AC: 3444 AN: 4830

European-Finnish (FIN) AF: 0.649 AC: 6862 AN: 10570

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40371 AN: 67966

Other (OTH) AF: 0.559 AC: 1182 AN: 2114

Alfa AF: 0.572 Hom.: 56028

Bravo AF: 0.541

Asia WGS AF: 0.618 AC: 2148 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.88
CADD	Benign	0.32
DANN	Benign	0.50
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs704624; hg19: chr11-130080017; COSMIC: COSV53835076;