Variant 7-101163186-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003378.4(VGF):c.1658G>A(p.Arg553Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,396,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

VGF
NM_003378.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35043073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VGF	NM_003378.4 linkuse as main transcript	c.1658G>A	p.Arg553Gln	missense_variant	2/2	ENST00000249330.3	NP_003369.2
VGF	XM_005250561.6 linkuse as main transcript	c.1658G>A	p.Arg553Gln	missense_variant	2/2		XP_005250618.1
VGF	XM_011516549.4 linkuse as main transcript	c.1658G>A	p.Arg553Gln	missense_variant	3/3		XP_011514851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VGF	ENST00000249330.3 linkuse as main transcript	c.1658G>A	p.Arg553Gln	missense_variant	2/2	1	NM_003378.4	ENSP00000249330	P1
VGF	ENST00000445482.2 linkuse as main transcript	c.1658G>A	p.Arg553Gln	missense_variant	2/2	5		ENSP00000400884	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000113

AC:

AN:

177668

Hom.:

AF XY:

0.0000204

AC XY:

AN XY:

98064

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000789

Gnomad SAS exome

AF:

0.0000508

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1396048

Hom.:

Cov.:

AF XY:

0.00000289

AC XY:

AN XY:

692876

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000394

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.1658G>A (p.R553Q) alteration is located in exon 2 (coding exon 1) of the VGF gene. This alteration results from a G to A substitution at nucleotide position 1658, causing the arginine (R) at amino acid position 553 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.66

.;T

M_CAP

Pathogenic

0.77

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

0.98

D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.13

Sift

Uncertain

0.015

D;D

Sift4G

Benign

0.20

T;T

Polyphen

1.0

D;D

Vest4

0.34

MutPred

0.17

Loss of catalytic residue at R553 (P = 0.0331);Loss of catalytic residue at R553 (P = 0.0331);

MVP

0.068

MPC

0.77

ClinPred

0.63

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over