Variant 17-4785622-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000328739.6(VMO1):c.349G>C(p.Gly117Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,612,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

VMO1
ENST00000328739.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.275

Variant links:

Genes affected

VMO1 (HGNC:30387): (vitelline membrane outer layer 1 homolog) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

VMO1 links:

Genome browser will be placed here

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=0.321823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VMO1	NM_182566.3 linkuse as main transcript	c.349G>C	p.Gly117Arg	missense_variant	3/3	ENST00000328739.6	NP_872372.1	Q7Z5L0-1
VMO1	NM_001144939.2 linkuse as main transcript	c.*40G>C		3_prime_UTR_variant	3/3		NP_001138411.1	Q7Z5L0-4
VMO1	NM_001144940.2 linkuse as main transcript	c.*20G>C		3_prime_UTR_variant	3/3		NP_001138412.1	Q7Z5L0-3
VMO1	NM_001144941.2 linkuse as main transcript	c.*20G>C		3_prime_UTR_variant	2/2		NP_001138413.1	Q7Z5L0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VMO1	ENST00000328739.6 linkuse as main transcript	c.349G>C	p.Gly117Arg	missense_variant	3/3	1	NM_182566.3	ENSP00000328397.5	Q7Z5L0-1
VMO1	ENST00000354194.4 linkuse as main transcript	c.*20G>C		3_prime_UTR_variant	2/2	1		ENSP00000346133.4	Q7Z5L0-2
VMO1	ENST00000441199.2 linkuse as main transcript	c.*40G>C		3_prime_UTR_variant	3/3	2		ENSP00000408166.2	Q7Z5L0-4
VMO1	ENST00000416307.6 linkuse as main transcript	c.*20G>C		3_prime_UTR_variant	3/3	2		ENSP00000390450.2	Q7Z5L0-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000282

AC:

AN:

248400

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

134650

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000382

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1459994

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726384

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 25, 2024

The c.349G>C (p.G117R) alteration is located in exon 3 (coding exon 3) of the VMO1 gene. This alteration results from a G to C substitution at nucleotide position 349, causing the glycine (G) at amino acid position 117 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.40

CADD

Benign

8.6

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.55

M_CAP

Benign

0.030

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

2.9

MutationTaster

Benign

0.92

D;D;D;D

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.095

Sift

Benign

0.039

Sift4G

Uncertain

0.0030

Polyphen

0.46

Vest4

0.25

MutPred

0.77

Gain of MoRF binding (P = 0.0482);

MVP

0.41

MPC

0.77

ClinPred

0.43

GERP RS

3.0

Varity_R

0.30

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over