7-101163337-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003378.4(VGF):​c.1507G>A​(p.Val503Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V503A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

VGF
NM_003378.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.598
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.050408095).
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VGFNM_003378.4 linkc.1507G>A p.Val503Ile missense_variant Exon 2 of 2 ENST00000249330.3 NP_003369.2 O15240
VGFXM_005250561.6 linkc.1507G>A p.Val503Ile missense_variant Exon 2 of 2 XP_005250618.1 O15240
VGFXM_011516549.4 linkc.1507G>A p.Val503Ile missense_variant Exon 3 of 3 XP_011514851.1 O15240

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VGFENST00000249330.3 linkc.1507G>A p.Val503Ile missense_variant Exon 2 of 2 1 NM_003378.4 ENSP00000249330.2 O15240
VGFENST00000445482.2 linkc.1507G>A p.Val503Ile missense_variant Exon 2 of 2 5 ENSP00000400884.2 O15240

Frequencies

GnomAD3 genomes
AF:
0.000554
AC:
6
AN:
10828
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.000792
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00138
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00248
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000334
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000128
AC:
1
AN:
78386
Hom.:
0
AF XY:
0.0000243
AC XY:
1
AN XY:
41152
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000856
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000336
AC:
8
AN:
237800
Hom.:
0
Cov.:
4
AF XY:
0.0000402
AC XY:
5
AN XY:
124292
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:
0.0000295
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000484
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000554
AC:
6
AN:
10832
Hom.:
0
Cov.:
0
AF XY:
0.000375
AC XY:
2
AN XY:
5332
show subpopulations
Gnomad4 AFR
AF:
0.000791
Gnomad4 AMR
AF:
0.00138
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00248
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000334
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 11, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1507G>A (p.V503I) 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 1507, causing the valine (V) at amino acid position 503 to be replaced by an isoleucine (I). 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
Benign
0.090
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
19
DANN
Benign
0.97
DEOGEN2
Benign
0.092
T;T
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.44
.;T
M_CAP
Pathogenic
0.57
D
MetaRNN
Benign
0.050
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
0.030
N;N
REVEL
Benign
0.10
Sift
Benign
0.23
T;T
Sift4G
Benign
0.30
T;T
Polyphen
0.0030
B;B
Vest4
0.089
MutPred
0.081
Loss of methylation at R504 (P = 0.1041);Loss of methylation at R504 (P = 0.1041);
MVP
0.043
MPC
0.54
ClinPred
0.074
T
GERP RS
1.3
Varity_R
0.088
gMVP
0.050

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

LitVar

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

Other links and lift over

dbSNP: rs1202377910; hg19: chr7-100806618; API