Genetic Variant NM_003378.4:c.1643A>C (chr7-101163201-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003378.4(VGF):c.1643A>C(p.Asn548Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000259 in 1,542,298 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N548S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

VGF
NM_003378.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.112

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18828124).

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.1643A>C	p.Asn548Thr	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.1643A>C	p.Asn548Thr	missense	Exon 2 of 2	ENSP00000249330.2	O15240
VGF	ENST00000445482.2	TSL:5	c.1643A>C	p.Asn548Thr	missense	Exon 2 of 2	ENSP00000400884.2	O15240
VGF	ENST00000970416.1		c.1643A>C	p.Asn548Thr	missense	Exon 2 of 2	ENSP00000640475.1

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000490

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000113

AC:

AN:

177498

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000897

Gnomad AMR exome

AF:

0.0000431

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:

0.00000144

AC:

AN:

1392068

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690422

show subpopulations

African (AFR)

AF:

0.0000350

AC:

AN:

28582

American (AMR)

AF:

0.0000302

AC:

AN:

33128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21592

East Asian (EAS)

AF:

0.00

AC:

AN:

36144

South Asian (SAS)

AF:

0.00

AC:

AN:

75266

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5464

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1084502

Other (OTH)

AF:

0.00

AC:

AN:

57190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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

AF:

0.0000133

AC:

AN:

150230

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73324

show subpopulations

African (AFR)

AF:

0.0000490

AC:

AN:

40822

American (AMR)

AF:

0.00

AC:

AN:

15172

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.00

AC:

AN:

5036

South Asian (SAS)

AF:

0.00

AC:

AN:

4748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67432

Other (OTH)

AF:

0.00

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.47

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.11

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.2

REVEL

Benign

0.14

Sift

Pathogenic

0.0

Sift4G

Benign

0.47

Polyphen

0.28

Vest4

0.36

MVP

0.043

MPC

0.68

ClinPred

0.14

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.34

gMVP

0.23

Mutation Taster

=96/4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over