Genetic Variant NM_021978.4:c.74G>A (chr11-130160053-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021978.4(ST14):c.74G>A(p.Arg25Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,282,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000031 ( 0 hom. )

Consequence

ST14
NM_021978.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

Publications

0 publications found

Variant links:

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

ST14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09754714).

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.74G>A	p.Arg25Gln	missense	Exon 1 of 19	NP_068813.1	Q9Y5Y6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ST14	ENST00000278742.6	TSL:1 MANE Select	c.74G>A	p.Arg25Gln	missense	Exon 1 of 19	ENSP00000278742.5	Q9Y5Y6
ST14	ENST00000894129.1		c.74G>A	p.Arg25Gln	missense	Exon 1 of 19	ENSP00000564188.1
ST14	ENST00000894128.1		c.74G>A	p.Arg25Gln	missense	Exon 1 of 19	ENSP00000564187.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000312

AC:

AN:

1282114

Hom.:

Cov.:

AF XY:

0.00000476

AC XY:

AN XY:

630636

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25984

American (AMR)

AF:

0.00

AC:

AN:

22758

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21710

East Asian (EAS)

AF:

0.00

AC:

AN:

27480

South Asian (SAS)

AF:

0.00

AC:

AN:

65086

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4202

European-Non Finnish (NFE)

AF:

0.00000393

AC:

AN:

1017744

Other (OTH)

AF:

0.00

AC:

AN:

51808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.85

MetaRNN

Benign

0.098

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.46

PhyloP100

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

0.10

REVEL

Benign

0.068

Sift

Benign

0.18

Sift4G

Benign

0.38

Polyphen

0.029

Vest4

0.10

MutPred

0.25

Loss of MoRF binding (P = 0.0299)

MVP

0.62

MPC

0.42

ClinPred

0.17

GERP RS

2.5

PromoterAI

0.031

Neutral

(source)

Varity_R

0.045

gMVP

0.21

Mutation Taster

=91/9

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over