chr7-101163294-C-T

Variant names:

• chr7-101163294-C-T
• rs201997904
• NM_003378.4:c.1550G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003378.4(VGF):​c.1550G>A​(p.Arg517Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 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: 𝑓 0.000011 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VGF NM_003378.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05170417).

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.1550G>A	p.Arg517Gln	missense	Exon 2 of 2	NP_003369.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VGF	ENST00000249330.3	TSL:1 MANE Select	c.1550G>A	p.Arg517Gln	missense	Exon 2 of 2	ENSP00000249330.2	O15240
	VGF	ENST00000445482.2	TSL:5	c.1550G>A	p.Arg517Gln	missense	Exon 2 of 2	ENSP00000400884.2	O15240
	VGF	ENST00000970416.1		c.1550G>A	p.Arg517Gln	missense	Exon 2 of 2	ENSP00000640475.1

Frequencies

GnomAD3 genomes AF: 0.0000105 AC: 1 AN: 95142 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000384

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1039742 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 509018

African (AFR) AF: 0.00 AC: 0 AN: 20862

American (AMR) AF: 0.00 AC: 0 AN: 21682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10466

East Asian (EAS) AF: 0.00 AC: 0 AN: 15292

South Asian (SAS) AF: 0.00 AC: 0 AN: 65500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2620

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 850382

Other (OTH) AF: 0.00 AC: 0 AN: 37684

GnomAD4 genome AF: 0.0000105 AC: 1 AN: 95142 Hom.: 0 Cov.: 20 AF XY: 0.0000228 AC XY: 1 AN XY: 43842

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24692

American (AMR) AF: 0.00 AC: 0 AN: 7360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2664

East Asian (EAS) AF: 0.00 AC: 0 AN: 2656

South Asian (SAS) AF: 0.000384 AC: 1 AN: 2606

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 156

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 49118

Other (OTH) AF: 0.00 AC: 0 AN: 1258

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.13
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.022
Sift	Benign	0.27	T
Sift4G	Benign	0.52	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.14		Loss of helix (P = 0.0558)
MVP		0.043
MPC		0.77
ClinPred		0.093	T
GERP RS		3.5
Varity_R		0.060
gMVP		0.078
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs201997904; hg19: chr7-100806575;