dbSNP rs567139324: VNN2:p.Leu412Val (chr6-132749832-A-C) – 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_004665.6(VNN2):c.1234T>G(p.Leu412Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

VNN2
NM_004665.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.97

Publications

0 publications found

Variant links:

Genes affected

VNN2 (HGNC:12706): (vanin 2) This gene product is a member of the Vanin family of proteins that 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. The encoded protein is a GPI-anchored cell surface molecule that plays a role in transendothelial migration of neutrophils. This gene lies in close proximity to, and in same transcriptional orientation as two other vanin genes on chromosome 6q23-q24. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2011]

VNN2 links:

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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=0.07705015).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004665.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VNN2	NM_004665.6	MANE Select	c.1234T>G	p.Leu412Val	missense	Exon 6 of 7	NP_004656.3
VNN2	NM_078488.3		c.1075T>G	p.Leu359Val	missense	Exon 7 of 8	NP_511043.2	O95498-6
VNN2	NM_001242350.3		c.571T>G	p.Leu191Val	missense	Exon 4 of 5	NP_001229279.2	O95498-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VNN2	ENST00000326499.11	TSL:1 MANE Select	c.1234T>G	p.Leu412Val	missense	Exon 6 of 7	ENSP00000322276.6	O95498-1
VNN2	ENST00000525289.5	TSL:1	c.571T>G	p.Leu191Val	missense	Exon 4 of 5	ENSP00000436935.1	O95498-2
VNN2	ENST00000392389.6	TSL:1	n.*357T>G		non_coding_transcript_exon	Exon 6 of 7	ENSP00000376190.2	J3QT03

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461768

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111944

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.0040

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.026

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.75

M_CAP

Benign

0.075

MetaRNN

Benign

0.077

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.4

PhyloP100

-2.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.9

REVEL

Benign

0.19

Sift

Benign

0.22

Sift4G

Benign

0.21

Polyphen

0.019

Vest4

0.073

MutPred

0.31

Loss of sheet (P = 0.0817)

MVP

0.17

MPC

0.022

ClinPred

0.094

GERP RS

-11

Varity_R

0.13

gMVP

0.53

Mutation Taster

=97/3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over