chr6-132694132-T-C

Variant names:

• chr6-132694132-T-C
• rs2272996
• NM_004666.3:c.392A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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.

• Frequency:
  • Genomes: 𝑓 0.24 (4693 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54777 hom.)
• Consequence: VNN1 NM_004666.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83
• Publications: 37 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004666.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VNN1	NM_004666.3	MANE Select	c.392A>G	p.Asn131Ser	missense	Exon 3 of 7	NP_004657.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VNN1	ENST00000367928.5	TSL:1 MANE Select	c.392A>G	p.Asn131Ser	missense	Exon 3 of 7	ENSP00000356905.4

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36609 AN: 151870 Hom.: 4699 Cov.: 32

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

GnomAD2 exomes AF: 0.266 AC: 66628 AN: 250754 AF XY: 0.271

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 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.: 35 AF XY: 0.271 AC XY: 196986 AN XY: 727022

African (AFR) AF: 0.184 AC: 6162 AN: 33474

American (AMR) AF: 0.179 AC: 7977 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 6917 AN: 26112

East Asian (EAS) AF: 0.405 AC: 16065 AN: 39684

South Asian (SAS) AF: 0.294 AC: 25323 AN: 86194

European-Finnish (FIN) AF: 0.276 AC: 14723 AN: 53410

Middle Eastern (MID) AF: 0.211 AC: 1215 AN: 5766

European-Non Finnish (NFE) AF: 0.271 AC: 301172 AN: 1111784

Other (OTH) AF: 0.262 AC: 15843 AN: 60384

GnomAD4 genome AF: 0.241 AC: 36609 AN: 151988 Hom.: 4693 Cov.: 32 AF XY: 0.242 AC XY: 17964 AN XY: 74282

African (AFR) AF: 0.191 AC: 7933 AN: 41438

American (AMR) AF: 0.180 AC: 2746 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 962 AN: 3466

East Asian (EAS) AF: 0.379 AC: 1959 AN: 5174

South Asian (SAS) AF: 0.296 AC: 1427 AN: 4824

European-Finnish (FIN) AF: 0.275 AC: 2906 AN: 10552

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17916 AN: 67968

Other (OTH) AF: 0.227 AC: 480 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0036	T
MetaSVM	Uncertain	0.36	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.8
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.34
Sift	Benign	0.034	D
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.24
MPC		0.23
ClinPred		0.028	T
GERP RS		6.1
Varity_R		0.60
gMVP		0.58
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2272996; hg19: chr6-133015271; COSMIC: COSV63389953; COSMIC: COSV63389953;