6-132751167-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004665.6(VNN2):c.1178G>A(p.Arg393Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,604,370 control chromosomes in the GnomAD database, including 18 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0061 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00083 (7 hom.)
• Consequence: VNN2 NM_004665.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0310

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003980994).
• BP6: Variant 6-132751167-C-T is Benign according to our data. Variant chr6-132751167-C-T is described in ClinVar as [Benign]. Clinvar id is 784097.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00611 (930/152328) while in subpopulation AFR AF= 0.0203 (843/41566). AF 95% confidence interval is 0.0191. There are 11 homozygotes in gnomad4. There are 435 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VNN2	NM_004665.6	c.1178G>A	p.Arg393Gln	missense_variant	5/7	ENST00000326499.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VNN2	ENST00000326499.11	c.1178G>A	p.Arg393Gln	missense_variant	5/7	1	NM_004665.6	P1

Frequencies

GnomAD3 genomes AF: 0.00610 AC: 929 AN: 152210 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00182 AC: 445 AN: 244510 Hom.: 6 AF XY: 0.00141 AC XY: 187 AN XY: 132198

Gnomad AFR exome AF: 0.0206

Gnomad AMR exome AF: 0.00170

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000554

Gnomad SAS exome AF: 0.000103

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000368

Gnomad OTH exome AF: 0.00204

GnomAD4 exome AF: 0.000831 AC: 1207 AN: 1452042 Hom.: 7 Cov.: 31 AF XY: 0.000754 AC XY: 544 AN XY: 721612

Gnomad4 AFR exome AF: 0.0219

Gnomad4 AMR exome AF: 0.00156

Gnomad4 ASJ exome AF: 0.0000391

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000472

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000265

Gnomad4 OTH exome AF: 0.00187

GnomAD4 genome AF: 0.00611 AC: 930 AN: 152328 Hom.: 11 Cov.: 32 AF XY: 0.00584 AC XY: 435 AN XY: 74488

Gnomad4 AFR AF: 0.0203

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00140 Hom.: 4

Bravo AF: 0.00669

ESP6500AA AF: 0.0209 AC: 92

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.00218 AC: 265

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000594

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.27
Cadd	Benign	14
Dann	Uncertain	0.99
DEOGEN2	Benign	0.019	T;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.26	T;T
MetaRNN	Benign	0.0040	T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.33	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.017	D;T
Sift4G	Uncertain	0.046	D;T
Polyphen		0.56	P;.
Vest4		0.18
MVP		0.49
MPC		0.032
ClinPred		0.0069	T
GERP RS		2.9
Varity_R		0.032
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

Other links and lift over

dbSNP: rs34856068; hg19: chr6-133072306;