7-101163294-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003378.4(VGF):​c.1550G>C​(p.Arg517Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000962 in 1,039,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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. R517L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 20)
Exomes š‘“: 9.6e-7 ( 0 hom. )

Consequence

VGF
NM_003378.4 missense

Scores

1
1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.126
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.097221345).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VGFNM_003378.4 linkc.1550G>C p.Arg517Pro missense_variant Exon 2 of 2 ENST00000249330.3 NP_003369.2 O15240
VGFXM_005250561.6 linkc.1550G>C p.Arg517Pro missense_variant Exon 2 of 2 XP_005250618.1 O15240
VGFXM_011516549.4 linkc.1550G>C p.Arg517Pro 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.1550G>C p.Arg517Pro missense_variant Exon 2 of 2 1 NM_003378.4 ENSP00000249330.2 O15240
VGFENST00000445482.2 linkc.1550G>C p.Arg517Pro missense_variant Exon 2 of 2 5 ENSP00000400884.2 O15240

Frequencies

GnomAD3 genomes
Cov.:
20
GnomAD4 exome
AF:
9.62e-7
AC:
1
AN:
1039744
Hom.:
0
Cov.:
36
AF XY:
0.00000196
AC XY:
1
AN XY:
509020
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000118
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.093
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
18
DANN
Benign
0.96
DEOGEN2
Benign
0.078
T;T
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.74
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.45
.;T
M_CAP
Uncertain
0.16
D
MetaRNN
Benign
0.097
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-0.27
N;N
REVEL
Benign
0.061
Sift
Benign
0.12
T;T
Sift4G
Benign
0.21
T;T
Polyphen
0.25
B;B
Vest4
0.25
MutPred
0.17
Loss of helix (P = 0.0076);Loss of helix (P = 0.0076);
MVP
0.043
MPC
0.96
ClinPred
0.13
T
GERP RS
3.5
Varity_R
0.15
gMVP
0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-100806575; API