Variant 6-132692437-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004666.3(VNN1):c.974C>A(p.Ala325Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,614,054 control chromosomes in the GnomAD database, including 276 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.023 ( 141 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 135 hom. )

Consequence

VNN1
NM_004666.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.589

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025770068).

BP6

Variant 6-132692437-G-T is Benign according to our data. Variant chr6-132692437-G-T is described in ClinVar as [Benign]. Clinvar id is 776158.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.079 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.974C>A	p.Ala325Glu	missense_variant	5/7	ENST00000367928.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VNN1	ENST00000367928.5 linkuse as main transcript	c.974C>A	p.Ala325Glu	missense_variant	5/7	1	NM_004666.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0233

AC:

3537

AN:

152124

Hom.:

138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0812

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00674

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:

0.000397

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.00583

AC:

1464

AN:

251040

Hom.:

AF XY:

0.00419

AC XY:

568

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.0805

Gnomad AMR exome

AF:

0.00341

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00242

AC:

3540

AN:

1461812

Hom.:

135

Cov.:

AF XY:

0.00209

AC XY:

1519

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0863

Gnomad4 AMR exome

AF:

0.00396

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000101

Gnomad4 OTH exome

AF:

0.00543

GnomAD4 genome

AF:

0.0233

AC:

3550

AN:

152242

Hom.:

141

Cov.:

AF XY:

0.0223

AC XY:

1657

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0813

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.00136

Hom.:

Bravo

AF:

0.0265

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0747

AC:

329

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00730

AC:

886

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.43

CADD

Benign

6.2

DANN

Benign

0.48

DEOGEN2

Benign

0.062

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.22

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

0.15

REVEL

Benign

0.20

Sift

Benign

0.35

Sift4G

Benign

0.71

Polyphen

0.012

Vest4

0.23

MVP

0.55

MPC

0.042

ClinPred

0.0081

GERP RS

4.0

Varity_R

0.11

gMVP

0.59

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over