Genetic Variant VGF:p.Glu525Lys (chr7-101163271-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003378.4(VGF):c.1573G>A(p.Glu525Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,358,558 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 28)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

VGF
NM_003378.4 missense

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2826392).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
VGF	NM_003378.4 link	c.1573G>A	p.Glu525Lys	missense_variant	Exon 2 of 2	ENST00000249330.3	NP_003369.2
VGF	XM_005250561.6 link	c.1573G>A	p.Glu525Lys	missense_variant	Exon 2 of 2		XP_005250618.1
VGF	XM_011516549.4 link	c.1573G>A	p.Glu525Lys	missense_variant	Exon 3 of 3		XP_011514851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VGF	ENST00000249330.3 link	c.1573G>A	p.Glu525Lys	missense_variant	Exon 2 of 2	1	NM_003378.4	ENSP00000249330.2
VGF	ENST00000445482.2 link	c.1573G>A	p.Glu525Lys	missense_variant	Exon 2 of 2	5		ENSP00000400884.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000147

AC:

AN:

1358558

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

668168

show subpopulations

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:

0.0000141

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:

9.37e-7

AC:

AN:

1067458

Other (OTH)

AF:

0.00

AC:

AN:

55858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.0015

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.64

.;T

M_CAP

Pathogenic

0.72

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.0

N;N

PhyloP100

1.9

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.37

N;N

REVEL

Benign

0.13

Sift

Uncertain

0.015

D;D

Sift4G

Benign

0.20

T;T

Polyphen

1.0

D;D

Vest4

0.38

MutPred

0.21

Gain of methylation at E525 (P = 0.0017);Gain of methylation at E525 (P = 0.0017);

MVP

0.068

MPC

0.75

ClinPred

0.55

GERP RS

4.6

Varity_R

0.33

gMVP

0.20

Mutation Taster

=95/5

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over