rs1334622920

Variant names:

• chr7-101163363-G-A
• NM_003378.4:c.1481C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-101163363-G-A
• chr7-101163363-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003378.4(VGF):​c.1481C>T​(p.Pro494Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,386,072 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. P494H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: VGF NM_003378.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.991

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

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=0.3921933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VGF	NM_003378.4	c.1481C>T	p.Pro494Leu	missense_variant	Exon 2 of 2	ENST00000249330.3	NP_003369.2
VGF	XM_005250561.6	c.1481C>T	p.Pro494Leu	missense_variant	Exon 2 of 2		XP_005250618.1
VGF	XM_011516549.4	c.1481C>T	p.Pro494Leu	missense_variant	Exon 3 of 3		XP_011514851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VGF	ENST00000249330.3	c.1481C>T	p.Pro494Leu	missense_variant	Exon 2 of 2	1	NM_003378.4	ENSP00000249330.2
VGF	ENST00000445482.2	c.1481C>T	p.Pro494Leu	missense_variant	Exon 2 of 2	5		ENSP00000400884.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1386072 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 682970

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: 0.0000252

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D;D
Eigen	Benign	0.17
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.56	.;T
M_CAP	Pathogenic	0.74	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-4.2	D;D
REVEL	Benign	0.14
Sift	Benign	0.037	D;D
Sift4G	Benign	0.076	T;T
Polyphen		0.97	D;D
Vest4		0.34
MutPred		0.13		Loss of glycosylation at P494 (P = 0.0195);Loss of glycosylation at P494 (P = 0.0195);
MVP		0.043
MPC		0.68
ClinPred		0.74	D
GERP RS		4.4
Varity_R		0.24
gMVP		0.13

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: chr7-100806644;