chr11-130188152-A-G

Variant names:

• chr11-130188152-A-G
• rs62642510
• NM_021978.4:c.120A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_021978.4(ST14):​c.120A>G​(p.Pro40Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0516 in 1,614,114 control chromosomes in the GnomAD database, including 4,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1863 hom., cov: 33)
  • Exomes 𝑓: 0.046 (2803 hom.)
• Consequence: ST14 NM_021978.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.81
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 11-130188152-A-G is Benign according to our data. Variant chr11-130188152-A-G is described in ClinVar as Benign. ClinVar VariationId is 1599867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.81 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 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.120A>G	p.Pro40Pro	synonymous	Exon 2 of 19	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.120A>G	p.Pro40Pro	synonymous	Exon 2 of 19	ENSP00000278742.5	Q9Y5Y6
	ST14	ENST00000894129.1		c.120A>G	p.Pro40Pro	synonymous	Exon 2 of 19	ENSP00000564188.1
	ST14	ENST00000894128.1		c.120A>G	p.Pro40Pro	synonymous	Exon 2 of 19	ENSP00000564187.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16425 AN: 152126 Hom.: 1851 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0649

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.0259

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0419

Gnomad OTH AF: 0.0995

GnomAD2 exomes AF: 0.0514 AC: 12912 AN: 251162 AF XY: 0.0458

Gnomad AFR exome AF: 0.292

Gnomad AMR exome AF: 0.0408

Gnomad ASJ exome AF: 0.0850

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0254

Gnomad NFE exome AF: 0.0418

Gnomad OTH exome AF: 0.0530

GnomAD4 exome AF: 0.0457 AC: 66857 AN: 1461870 Hom.: 2803 Cov.: 32 AF XY: 0.0441 AC XY: 32093 AN XY: 727234

African (AFR) AF: 0.294 AC: 9854 AN: 33480

American (AMR) AF: 0.0443 AC: 1982 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 2205 AN: 26136

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.00931 AC: 803 AN: 86258

European-Finnish (FIN) AF: 0.0252 AC: 1347 AN: 53418

Middle Eastern (MID) AF: 0.0539 AC: 311 AN: 5768

European-Non Finnish (NFE) AF: 0.0423 AC: 46997 AN: 1112000

Other (OTH) AF: 0.0555 AC: 3352 AN: 60394

GnomAD4 genome AF: 0.108 AC: 16486 AN: 152244 Hom.: 1863 Cov.: 33 AF XY: 0.104 AC XY: 7714 AN XY: 74454

African (AFR) AF: 0.283 AC: 11753 AN: 41506

American (AMR) AF: 0.0648 AC: 992 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0905 AC: 314 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.00891 AC: 43 AN: 4824

European-Finnish (FIN) AF: 0.0259 AC: 275 AN: 10620

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0419 AC: 2850 AN: 68028

Other (OTH) AF: 0.105 AC: 222 AN: 2112

Alfa AF: 0.0599 Hom.: 309

Bravo AF: 0.120

Asia WGS AF: 0.0390 AC: 137 AN: 3478

EpiCase AF: 0.0433

EpiControl AF: 0.0453

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	-0.94
CADD	Benign	0.0020
DANN	Benign	0.44
PhyloP100		-3.8
Mutation Taster		=99/1	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: rs62642510; hg19: chr11-130058047;