chr11-130160000-C-T

Variant names:

• chr11-130160000-C-T
• rs372702262
• NM_021978.4:c.21C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_021978.4(ST14):​c.21C>T​(p.Arg7Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000497 in 1,414,390 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (7 hom.)
• Consequence: ST14 NM_021978.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00500
• Publications: 0 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=-0.65).
• BP6: Variant 11-130160000-C-T is Benign according to our data. Variant chr11-130160000-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 2038778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.005 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00192 (291/151830) while in subpopulation AFR AF = 0.00645 (267/41408). AF 95% confidence interval is 0.00581. There are 1 homozygotes in GnomAd4. There are 135 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

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.21C>T	p.Arg7Arg	synonymous	Exon 1 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.21C>T	p.Arg7Arg	synonymous	Exon 1 of 19	ENSP00000278742.5	Q9Y5Y6
	ST14	ENST00000894129.1		c.21C>T	p.Arg7Arg	synonymous	Exon 1 of 19	ENSP00000564188.1
	ST14	ENST00000894128.1		c.21C>T	p.Arg7Arg	synonymous	Exon 1 of 19	ENSP00000564187.1

Frequencies

GnomAD3 genomes AF: 0.00192 AC: 291 AN: 151722 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00647

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.000233 AC: 17 AN: 73110 AF XY: 0.000262

Gnomad AFR exome AF: 0.00743

Gnomad AMR exome AF: 0.000465

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000125

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000326 AC: 412 AN: 1262560 Hom.: 7 Cov.: 30 AF XY: 0.000331 AC XY: 205 AN XY: 619454

African (AFR) AF: 0.00821 AC: 210 AN: 25592

American (AMR) AF: 0.000430 AC: 9 AN: 20930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21054

East Asian (EAS) AF: 0.00 AC: 0 AN: 27218

South Asian (SAS) AF: 0.0000325 AC: 2 AN: 61568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44400

Middle Eastern (MID) AF: 0.00241 AC: 10 AN: 4152

European-Non Finnish (NFE) AF: 0.000106 AC: 107 AN: 1006850

Other (OTH) AF: 0.00146 AC: 74 AN: 50796

GnomAD4 genome AF: 0.00192 AC: 291 AN: 151830 Hom.: 1 Cov.: 32 AF XY: 0.00182 AC XY: 135 AN XY: 74212

African (AFR) AF: 0.00645 AC: 267 AN: 41408

American (AMR) AF: 0.000786 AC: 12 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5096

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67912

Other (OTH) AF: 0.00238 AC: 5 AN: 2102

Alfa AF: 0.000145 Hom.: 0

Bravo AF: 0.00217

Asia WGS AF: 0.000580 AC: 2 AN: 3460

ClinVar

ClinVar submissions

Significance: Benign/Likely 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	-0.65
CADD	Benign	9.9
DANN	Benign	0.94
PhyloP100		0.0050
PromoterAI		-0.032	Neutral
Mutation Taster		=100/0	polymorphism

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: rs372702262; hg19: chr11-130029895;