NM_000638.4:c.1199C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000638.4(VTN):c.1199C>T(p.Thr400Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,613,858 control chromosomes in the GnomAD database, including 196,068 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.51 ( 20437 hom., cov: 33)

Exomes 𝑓: 0.49 ( 175631 hom. )

Consequence

VTN
NM_000638.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.85

Publications

89 publications found

Variant links:

Genes affected

VTN (HGNC:12724): (vitronectin) The protein encoded by this gene functions in part as an adhesive glycoprotein. Differential expression of this protein can promote either cell adhesion or migration as it links cells to the extracellular matrix through a variety of ligands. These ligands include integrins, plasminogen activator inhibitor-1, and urokinase plasminogen activator receptor. This secreted protein can be present in the plasma as a monomer or dimer and forms a multimer in the extracellular matrix of several tissues. This protein also inhibits the membrane-damaging effect of the terminal cytolytic complement pathway and binds to several serpin serine protease inhibitors. This protein can also promote extracellular matrix degradation and thus plays a role in tumorigenesis. It is involved in a variety of other biological processes such as the regulation of the coagulation pathway, wound healing, and tissue remodeling. The heparin-binding domain of this protein give it anti-microbial properties. It is also a lipid binding protein that forms a principal component of high density lipoprotein. [provided by RefSeq, Aug 2020]

VTN links:

ENSG00000273171 (HGNC:):

ENSG00000273171 links:

SARM1 (HGNC:17074): (sterile alpha and TIR motif containing 1) Enables NAD+ nucleotidase, cyclic ADP-ribose generating and identical protein binding activity. Involved in NAD catabolic process; positive regulation of neuron death; and response to axon injury. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

SARM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.3920254E-6).

BP6

Variant 17-28367840-G-A is Benign according to our data. Variant chr17-28367840-G-A is described in ClinVar as [Benign]. Clinvar id is 3059155.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTN	NM_000638.4 link	c.1199C>T	p.Thr400Met	missense_variant	Exon 7 of 8	ENST00000226218.9	NP_000629.3	P04004D9ZGG2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTN	ENST00000226218.9 link	c.1199C>T	p.Thr400Met	missense_variant	Exon 7 of 8	1	NM_000638.4	ENSP00000226218.4		P04004
ENSG00000273171	ENST00000555059.2 link	c.173C>T	p.Thr58Met	missense_variant	Exon 1 of 4	4		ENSP00000452347.3		H0YJW9

Frequencies

GnomAD3 genomes

AF:

0.515

AC:

78324

AN:

152040

Hom.:

20437

Cov.:

show subpopulations

Gnomad AFR

AF:

0.571

Gnomad AMI

AF:

0.516

Gnomad AMR

AF:

0.555

Gnomad ASJ

AF:

0.468

Gnomad EAS

AF:

0.723

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.406

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.479

Gnomad OTH

AF:

0.524

GnomAD2 exomes

AF:

0.509

AC:

126472

AN:

248412

AF XY:

0.503

show subpopulations

Gnomad AFR exome

AF:

0.572

Gnomad AMR exome

AF:

0.572

Gnomad ASJ exome

AF:

0.478

Gnomad EAS exome

AF:

0.726

Gnomad FIN exome

AF:

0.415

Gnomad NFE exome

AF:

0.475

Gnomad OTH exome

AF:

0.492

GnomAD4 exome

AF:

0.487

AC:

711439

AN:

1461700

Hom.:

175631

Cov.:

AF XY:

0.486

AC XY:

353139

AN XY:

727148

show subpopulations

African (AFR)

AF:

0.568

AC:

19000

AN:

33478

American (AMR)

AF:

0.570

AC:

25468

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

12437

AN:

26134

East Asian (EAS)

AF:

0.747

AC:

29667

AN:

39698

South Asian (SAS)

AF:

0.476

AC:

41023

AN:

86256

European-Finnish (FIN)

AF:

0.416

AC:

22196

AN:

53326

Middle Eastern (MID)

AF:

0.479

AC:

2763

AN:

5768

European-Non Finnish (NFE)

AF:

0.475

AC:

528714

AN:

1111938

Other (OTH)

AF:

0.500

AC:

30171

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

24205

48410

72614

96819

121024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.515

AC:

78355

AN:

152158

Hom.:

20437

Cov.:

AF XY:

0.513

AC XY:

38131

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.571

AC:

23691

AN:

41506

American (AMR)

AF:

0.556

AC:

8503

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.468

AC:

1625

AN:

3470

East Asian (EAS)

AF:

0.723

AC:

3735

AN:

5164

South Asian (SAS)

AF:

0.470

AC:

2267

AN:

4828

European-Finnish (FIN)

AF:

0.406

AC:

4296

AN:

10592

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.479

AC:

32529

AN:

67978

Other (OTH)

AF:

0.520

AC:

1100

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2017

4033

6050

8066

10083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.493

Hom.:

54909

Bravo

AF:

0.533

TwinsUK

AF:

0.477

AC:

1768

ALSPAC

AF:

0.450

AC:

1736

ESP6500AA

AF:

0.566

AC:

2493

ESP6500EA

AF:

0.481

AC:

4134

ExAC

AF:

0.507

AC:

61511

Asia WGS

AF:

0.525

AC:

1828

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

VTN-related disorder

Benign:1

Oct 30, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.0060

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.26

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.33

T;T

MetaRNN

Benign

0.0000044

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.69

.;N

PhyloP100

-2.8

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.47

.;N

REVEL

Benign

0.24

Sift

Benign

0.22

.;T

Sift4G

Benign

0.10

T;T

Polyphen

0.94

.;P

Vest4

0.053

MPC

0.22

ClinPred

0.023

GERP RS

-8.9

PromoterAI

0.047

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.021

gMVP

0.29

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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.

NM_000638.4:c.1199C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over