Genetic Variant VGF:p.Glu519* (chr7-101163289-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003378.4(VGF):c.1555G>T(p.Glu519*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000784 in 127,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000078 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

VGF
NM_003378.4 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.94

Publications

0 publications found

Variant links:

Genes affected

VGF (HGNC:12684): (VGF nerve growth factor inducible) This gene is specifically expressed in a subpopulation of neuroendocrine cells, and is upregulated by nerve growth factor. The structural organization of this gene is similar to that of the rat gene, and both the translated and the untranslated regions show a high degree of sequence similarity to the rat gene. The encoded secretory protein also shares similarities with the secretogranin/chromogranin family, however, its exact function is not known. [provided by RefSeq, Jul 2008]

VGF links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003378.4. 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
	VGF	NM_003378.4	MANE Select	c.1555G>T	p.Glu519*	stop_gained	Exon 2 of 2	NP_003369.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VGF	ENST00000249330.3	TSL:1 MANE Select	c.1555G>T	p.Glu519*	stop_gained	Exon 2 of 2	ENSP00000249330.2	O15240
VGF	ENST00000445482.2	TSL:5	c.1555G>T	p.Glu519*	stop_gained	Exon 2 of 2	ENSP00000400884.2	O15240
VGF	ENST00000970416.1		c.1555G>T	p.Glu519*	stop_gained	Exon 2 of 2	ENSP00000640475.1

Frequencies

GnomAD3 genomes

AF:

0.00000784

AC:

AN:

127528

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000272

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1243006

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

609972

African (AFR)

AF:

0.00

AC:

AN:

26180

American (AMR)

AF:

0.00

AC:

AN:

26658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16210

East Asian (EAS)

AF:

0.00

AC:

AN:

28464

South Asian (SAS)

AF:

0.00

AC:

AN:

69158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27940

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3732

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

995870

Other (OTH)

AF:

0.00

AC:

AN:

48794

GnomAD4 genome

AF:

0.00000784

AC:

AN:

127598

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

60730

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

34026

American (AMR)

AF:

0.00

AC:

AN:

11616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3244

East Asian (EAS)

AF:

0.00

AC:

AN:

3758

South Asian (SAS)

AF:

0.000272

AC:

AN:

3678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6930

Middle Eastern (MID)

AF:

0.00

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

61592

Other (OTH)

AF:

0.00

AC:

AN:

1724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.52

BayesDel_noAF

Pathogenic

0.51

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.36

PhyloP100

2.9

Vest4

0.70

GERP RS

3.7

Mutation Taster

=95/105

disease causing

(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