Variant 17-4785999-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_182566.3(VMO1):c.249G>C(p.Arg83Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,886 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: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

VMO1
NM_182566.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.430

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.821

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VMO1	NM_182566.3 linkuse as main transcript	c.249G>C	p.Arg83Ser	missense_variant	2/3	ENST00000328739.6	NP_872372.1
VMO1	NM_001144939.2 linkuse as main transcript	c.249G>C	p.Arg83Ser	missense_variant	2/3		NP_001138411.1
VMO1	NM_001144940.2 linkuse as main transcript	c.249G>C	p.Arg83Ser	missense_variant	2/3		NP_001138412.1
VMO1	NM_001144941.2 linkuse as main transcript	c.195+159G>C		intron_variant			NP_001138413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VMO1	ENST00000328739.6 linkuse as main transcript	c.249G>C	p.Arg83Ser	missense_variant	2/3	1	NM_182566.3	ENSP00000328397	P1	Q7Z5L0-1
VMO1	ENST00000354194.4 linkuse as main transcript	c.195+159G>C		intron_variant		1		ENSP00000346133		Q7Z5L0-2
VMO1	ENST00000441199.2 linkuse as main transcript	c.249G>C	p.Arg83Ser	missense_variant	2/3	2		ENSP00000408166		Q7Z5L0-4
VMO1	ENST00000416307.6 linkuse as main transcript	c.249G>C	p.Arg83Ser	missense_variant	2/3	2		ENSP00000390450		Q7Z5L0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251452

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135912

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:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727240

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:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 07, 2024

The c.249G>C (p.R83S) alteration is located in exon 2 (coding exon 2) of the VMO1 gene. This alteration results from a G to C substitution at nucleotide position 249, causing the arginine (R) at amino acid position 83 to be replaced by a serine (S). 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

0.81

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.090

.;.;T

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.030

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.054

MetaRNN

Pathogenic

0.82

D;D;D

MetaSVM

Benign

-0.78

MutationAssessor

Pathogenic

3.5

M;M;M

MutationTaster

Benign

0.64

D;D;D;D

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-4.2

D;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.012

D;D;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.73

MutPred

0.67

Loss of methylation at R83 (P = 0.0467);Loss of methylation at R83 (P = 0.0467);Loss of methylation at R83 (P = 0.0467);

MVP

0.46

MPC

1.3

ClinPred

0.98

GERP RS

1.4

Varity_R

0.82

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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