Variant 17-4786025-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000328739.6(VMO1):c.223G>T(p.Asp75Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,882 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: 6.8e-7 ( 0 hom. )

Consequence

VMO1
ENST00000328739.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.10

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.99

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VMO1	NM_182566.3 linkuse as main transcript	c.223G>T	p.Asp75Tyr	missense_variant	2/3	ENST00000328739.6	NP_872372.1	Q7Z5L0-1
VMO1	NM_001144939.2 linkuse as main transcript	c.223G>T	p.Asp75Tyr	missense_variant	2/3		NP_001138411.1	Q7Z5L0-4
VMO1	NM_001144940.2 linkuse as main transcript	c.223G>T	p.Asp75Tyr	missense_variant	2/3		NP_001138412.1	Q7Z5L0-3
VMO1	NM_001144941.2 linkuse as main transcript	c.195+133G>T		intron_variant			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.223G>T	p.Asp75Tyr	missense_variant	2/3	1	NM_182566.3	ENSP00000328397.5	Q7Z5L0-1
VMO1	ENST00000354194.4 linkuse as main transcript	c.195+133G>T		intron_variant		1		ENSP00000346133.4	Q7Z5L0-2
VMO1	ENST00000441199.2 linkuse as main transcript	c.223G>T	p.Asp75Tyr	missense_variant	2/3	2		ENSP00000408166.2	Q7Z5L0-4
VMO1	ENST00000416307.6 linkuse as main transcript	c.223G>T	p.Asp75Tyr	missense_variant	2/3	2		ENSP00000390450.2	Q7Z5L0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727236

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

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

Mar 01, 2024

The c.223G>T (p.D75Y) alteration is located in exon 2 (coding exon 2) of the VMO1 gene. This alteration results from a G to T substitution at nucleotide position 223, causing the aspartic acid (D) at amino acid position 75 to be replaced by a tyrosine (Y). 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

0.77

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.24

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

.;.;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.99

D;D;D

MetaSVM

Uncertain

-0.14

MutationAssessor

Pathogenic

3.8

H;H;H

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-8.2

D;D;D

REVEL

Uncertain

0.62

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.97

MutPred

0.91

Loss of disorder (P = 0.0213);Loss of disorder (P = 0.0213);Loss of disorder (P = 0.0213);

MVP

0.79

MPC

1.5

ClinPred

1.0

GERP RS

4.4

Varity_R

0.89

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over