Variant 6-132694132-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004666.3(VNN1):c.392A>G(p.Asn131Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,613,480 control chromosomes in the GnomAD database, including 59,470 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.24 ( 4693 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54777 hom. )

Consequence

VNN1
NM_004666.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.83

Variant links:

Genes affected

VNN1 (HGNC:12705): (vanin 1) This gene encodes a member of the vanin family of proteins, which share extensive sequence similarity with each other, and also with biotinidase. The family includes secreted and membrane-associated proteins, a few of which have been reported to participate in hematopoietic cell trafficking. No biotinidase activity has been demonstrated for any of the vanin proteins, however, they possess pantetheinase activity, which may play a role in oxidative-stress response. This protein, like its mouse homolog, is likely a GPI-anchored cell surface molecule. The mouse protein is expressed by the perivascular thymic stromal cells and regulates migration of T-cell progenitors to the thymus. This gene lies in close proximity to, and in the same transcriptional orientation as, two other vanin genes on chromosome 6q23-q24. [provided by RefSeq, Feb 2009]

VNN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035597682).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VNN1	NM_004666.3 linkuse as main transcript	c.392A>G	p.Asn131Ser	missense_variant	3/7	ENST00000367928.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VNN1	ENST00000367928.5 linkuse as main transcript	c.392A>G	p.Asn131Ser	missense_variant	3/7	1	NM_004666.3	P1

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36609

AN:

151870

Hom.:

4699

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.379

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.228

GnomAD3 exomes

AF:

0.266

AC:

66628

AN:

250754

Hom.:

9347

AF XY:

0.271

AC XY:

36701

AN XY:

135484

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.179

Gnomad ASJ exome

AF:

0.262

Gnomad EAS exome

AF:

0.388

Gnomad SAS exome

AF:

0.299

Gnomad FIN exome

AF:

0.273

Gnomad NFE exome

AF:

0.274

Gnomad OTH exome

AF:

0.253

GnomAD4 exome

AF:

0.271

AC:

395397

AN:

1461492

Hom.:

54777

Cov.:

AF XY:

0.271

AC XY:

196986

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.184

Gnomad4 AMR exome

AF:

0.179

Gnomad4 ASJ exome

AF:

0.265

Gnomad4 EAS exome

AF:

0.405

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.276

Gnomad4 NFE exome

AF:

0.271

Gnomad4 OTH exome

AF:

0.262

GnomAD4 genome

AF:

0.241

AC:

36609

AN:

151988

Hom.:

4693

Cov.:

AF XY:

0.242

AC XY:

17964

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.180

Gnomad4 ASJ

AF:

0.278

Gnomad4 EAS

AF:

0.379

Gnomad4 SAS

AF:

0.296

Gnomad4 FIN

AF:

0.275

Gnomad4 NFE

AF:

0.264

Gnomad4 OTH

AF:

0.227

Alfa

AF:

0.249

Hom.:

2198

Bravo

AF:

0.233

TwinsUK

AF:

0.265

AC:

983

ALSPAC

AF:

0.269

AC:

1036

ESP6500AA

AF:

0.191

AC:

840

ESP6500EA

AF:

0.270

AC:

2320

ExAC

AF:

0.272

AC:

32968

Asia WGS

AF:

0.298

AC:

1035

AN:

3478

EpiCase

AF:

0.269

EpiControl

AF:

0.265

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0036

MetaSVM

Uncertain

0.36

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

0.028

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.34

Sift

Benign

0.034

Sift4G

Benign

0.17

Polyphen

1.0

Vest4

0.24

MPC

0.23

ClinPred

0.028

GERP RS

6.1

Varity_R

0.60

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over