NM_021978.4:c.36C>T

Variant names:

• chr11-130160015-C-T
• rs781717480
• NM_021978.4:c.36C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_021978.4(ST14):​c.36C>T​(p.Gly12Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000035 in 1,428,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: ST14 NM_021978.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.449
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 11-130160015-C-T is Benign according to our data. Variant chr11-130160015-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2165215.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.449 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.36C>T	p.Gly12Gly	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.36C>T	p.Gly12Gly	synonymous	Exon 1 of 19	ENSP00000278742.5	Q9Y5Y6
	ST14	ENST00000894129.1		c.36C>T	p.Gly12Gly	synonymous	Exon 1 of 19	ENSP00000564188.1
	ST14	ENST00000894128.1		c.36C>T	p.Gly12Gly	synonymous	Exon 1 of 19	ENSP00000564187.1

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151760 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.000481

GnomAD2 exomes AF: 0.0000129 AC: 1 AN: 77246 AF XY: 0.0000228

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000345 AC: 44 AN: 1276174 Hom.: 0 Cov.: 30 AF XY: 0.0000399 AC XY: 25 AN XY: 627234

African (AFR) AF: 0.00 AC: 0 AN: 25864

American (AMR) AF: 0.0000453 AC: 1 AN: 22098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21534

East Asian (EAS) AF: 0.00 AC: 0 AN: 27388

South Asian (SAS) AF: 0.0000156 AC: 1 AN: 63920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4288

European-Non Finnish (NFE) AF: 0.0000394 AC: 40 AN: 1014518

Other (OTH) AF: 0.0000388 AC: 2 AN: 51552

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 151868 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74228

African (AFR) AF: 0.0000241 AC: 1 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5098

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67918

Other (OTH) AF: 0.000476 AC: 1 AN: 2100

Alfa AF: 0.0000628 Hom.: 0

Bravo AF: 0.0000416

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.96
PhyloP100		0.45
PromoterAI		-0.10	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: rs781717480; hg19: chr11-130029910;