NM_004665.6:c.1552G>A

Variant names:

• chr6-132744311-C-T
• NM_004665.6:c.1552G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004665.6(VNN2):​c.1552G>A​(p.Val518Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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)
• Consequence: VNN2 NM_004665.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.182
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06351587).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VNN2	NM_004665.6	MANE Select	c.1552G>A	p.Val518Ile	missense	Exon 7 of 7	NP_004656.3
	VNN2	NM_078488.3		c.1393G>A	p.Val465Ile	missense	Exon 8 of 8	NP_511043.2	O95498-6
	VNN2	NM_001242350.3		c.889G>A	p.Val297Ile	missense	Exon 5 of 5	NP_001229279.2	O95498-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VNN2	ENST00000326499.11	TSL:1 MANE Select	c.1552G>A	p.Val518Ile	missense	Exon 7 of 7	ENSP00000322276.6	O95498-1
	VNN2	ENST00000525289.5	TSL:1	c.889G>A	p.Val297Ile	missense	Exon 5 of 5	ENSP00000436935.1	O95498-2
	VNN2	ENST00000392389.6	TSL:1	n.*675G>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000376190.2	J3QT03

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	4.1
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.18
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.13
Sift	Benign	0.15	T
Sift4G	Benign	0.15	T
Polyphen		0.0030	B
Vest4		0.14
MutPred		0.18		Gain of helix (P = 0.0696)
MVP		0.23
MPC		0.027
ClinPred		0.035	T
GERP RS		1.0
Varity_R		0.038
gMVP		0.15
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr6-133065450;