dbSNP rs551062770: VGF:p.Pro542Leu (chr7-101163219-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_003378.4(VGF):c.1625C>T(p.Pro542Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,381,924 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. P542Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

VGF
NM_003378.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0360

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=0.33997035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VGF	NM_003378.4 link	c.1625C>T	p.Pro542Leu	missense_variant	Exon 2 of 2	ENST00000249330.3	NP_003369.2	O15240
VGF	XM_005250561.6 link	c.1625C>T	p.Pro542Leu	missense_variant	Exon 2 of 2		XP_005250618.1	O15240
VGF	XM_011516549.4 link	c.1625C>T	p.Pro542Leu	missense_variant	Exon 3 of 3		XP_011514851.1	O15240

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VGF	ENST00000249330.3 link	c.1625C>T	p.Pro542Leu	missense_variant	Exon 2 of 2	1	NM_003378.4	ENSP00000249330.2		O15240
VGF	ENST00000445482.2 link	c.1625C>T	p.Pro542Leu	missense_variant	Exon 2 of 2	5		ENSP00000400884.2		O15240

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000114

AC:

AN:

174742

Hom.:

AF XY:

0.0000105

AC XY:

AN XY:

95176

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:

0.000112

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000289

AC:

AN:

1381924

Hom.:

Cov.:

AF XY:

0.00000440

AC XY:

AN XY:

682300

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:

0.0000270

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.28e-7

Gnomad4 OTH exome

AF:

0.0000176

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000166

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;T

Eigen

Benign

-0.0088

Eigen_PC

Benign

-0.033

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.55

.;T

M_CAP

Pathogenic

0.80

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.0

N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.26

Sift

Benign

0.11

T;T

Sift4G

Benign

0.099

T;T

Polyphen

1.0

D;D

Vest4

0.29

MutPred

0.21

Loss of glycosylation at P542 (P = 0.0575);Loss of glycosylation at P542 (P = 0.0575);

MVP

0.043

MPC

0.68

ClinPred

0.46

GERP RS

3.4

Varity_R

0.063

gMVP

0.15

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over