rs372702262

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-130160000-C-G
• chr11-130160000-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_021978.4(ST14):​c.21C>G​(p.Arg7Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000792 in 1,262,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R7R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: ST14 NM_021978.4 synonymous
• Clinical Significance: Not reported in ClinVar
• 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, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=0.005 with no splicing effect.

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.92e-7 AC: 1 AN: 1262562 Hom.: 0 Cov.: 30 AF XY: 0.00000161 AC XY: 1 AN XY: 619456

African (AFR) AF: 0.00 AC: 0 AN: 25592

American (AMR) AF: 0.00 AC: 0 AN: 20930

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

East Asian (EAS) AF: 0.0000367 AC: 1 AN: 27218

South Asian (SAS) AF: 0.00 AC: 0 AN: 61568

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4152

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1006852

Other (OTH) AF: 0.00 AC: 0 AN: 50796

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.2
DANN	Benign	0.71
PhyloP100		0.0050
PromoterAI		0.13	Neutral

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;