dbSNP rs35400704: VGF:p.Glu525* (chr7-101163271-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.1573G>T(p.Glu525*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 28)

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: 1.89

Publications

4 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;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VGF	NM_003378.4 link	c.1573G>T	p.Glu525*	stop_gained	Exon 2 of 2	ENST00000249330.3	NP_003369.2	O15240
VGF	XM_005250561.6 link	c.1573G>T	p.Glu525*	stop_gained	Exon 2 of 2		XP_005250618.1	O15240
VGF	XM_011516549.4 link	c.1573G>T	p.Glu525*	stop_gained	Exon 3 of 3		XP_011514851.1	O15240

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VGF	ENST00000249330.3 link	c.1573G>T	p.Glu525*	stop_gained	Exon 2 of 2	1	NM_003378.4	ENSP00000249330.2		O15240
VGF	ENST00000445482.2 link	c.1573G>T	p.Glu525*	stop_gained	Exon 2 of 2	5		ENSP00000400884.2		O15240

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1358558

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

668168

African (AFR)

AF:

0.00

AC:

AN:

29146

American (AMR)

AF:

0.00

AC:

AN:

30464

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19932

East Asian (EAS)

AF:

0.00

AC:

AN:

37500

South Asian (SAS)

AF:

0.00

AC:

AN:

71128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42280

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4792

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1067458

Other (OTH)

AF:

0.00

AC:

AN:

55858

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.62

BayesDel_noAF

Pathogenic

0.66

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Benign

0.58

PhyloP100

1.9

Vest4

0.75

GERP RS

4.6

Mutation Taster

=58/142

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over