Genetic Variant NM_003378.4:c.1564G>T (chr7-101163280-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.1564G>T(p.Asp522Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000737 in 1,357,468 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 27)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

VGF
NM_003378.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

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.1564G>T	p.Asp522Tyr	missense	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.1564G>T	p.Asp522Tyr	missense	Exon 2 of 2	ENSP00000249330.2	O15240
VGF	ENST00000445482.2	TSL:5	c.1564G>T	p.Asp522Tyr	missense	Exon 2 of 2	ENSP00000400884.2	O15240
VGF	ENST00000970416.1		c.1564G>T	p.Asp522Tyr	missense	Exon 2 of 2	ENSP00000640475.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

151032

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.37e-7

AC:

AN:

1357468

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

667542

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29192

American (AMR)

AF:

0.00

AC:

AN:

30380

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20000

East Asian (EAS)

AF:

0.00

AC:

AN:

37644

South Asian (SAS)

AF:

0.00

AC:

AN:

70910

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40344

Middle Eastern (MID)

AF:

0.000216

AC:

AN:

4630

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1068442

Other (OTH)

AF:

0.00

AC:

AN:

55926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.87

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-0.62

MutationAssessor

Benign

0.0

PhyloP100

3.9

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.79

REVEL

Benign

0.14

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.37

MutPred

0.18

Gain of phosphorylation at D522 (P = 0.0084)

MVP

0.068

MPC

0.82

ClinPred

0.64

GERP RS

4.6

Varity_R

0.30

gMVP

0.19

Mutation Taster

=89/11

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over