Variant 17-4785399-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000328739.6(VMO1):c.572C>A(p.Ala191Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

VMO1
ENST00000328739.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VMO1	NM_182566.3 linkuse as main transcript	c.572C>A	p.Ala191Glu	missense_variant	3/3	ENST00000328739.6	NP_872372.1	Q7Z5L0-1
VMO1	NM_001144939.2 linkuse as main transcript	c.*263C>A		3_prime_UTR_variant	3/3		NP_001138411.1	Q7Z5L0-4
VMO1	NM_001144940.2 linkuse as main transcript	c.*243C>A		3_prime_UTR_variant	3/3		NP_001138412.1	Q7Z5L0-3
VMO1	NM_001144941.2 linkuse as main transcript	c.*243C>A		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.572C>A	p.Ala191Glu	missense_variant	3/3	1	NM_182566.3	ENSP00000328397.5	Q7Z5L0-1
VMO1	ENST00000354194.4 linkuse as main transcript	c.*243C>A		3_prime_UTR_variant	2/2	1		ENSP00000346133.4	Q7Z5L0-2
VMO1	ENST00000441199.2 linkuse as main transcript	c.*263C>A		3_prime_UTR_variant	3/3	2		ENSP00000408166.2	Q7Z5L0-4
VMO1	ENST00000416307.6 linkuse as main transcript	c.*243C>A		3_prime_UTR_variant	3/3	2		ENSP00000390450.2	Q7Z5L0-3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.0000200

AC:

AN:

250268

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135474

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000684

AC:

AN:

1461422

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000989

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000247

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

Apr 07, 2023

The c.572C>A (p.A191E) alteration is located in exon 3 (coding exon 3) of the VMO1 gene. This alteration results from a C to A substitution at nucleotide position 572, causing the alanine (A) at amino acid position 191 to be replaced by a glutamic acid (E). 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

Pathogenic

0.78

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.070

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-0.34

MutationAssessor

Pathogenic

3.4

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.38

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.79

MVP

0.68

MPC

1.4

ClinPred

0.93

GERP RS

3.8

Varity_R

0.79

gMVP

0.97

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over