Variant 17-4785547-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_182566.3(VMO1):c.424G>A(p.Val142Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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
NM_182566.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.667

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 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=0.37076175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VMO1	NM_182566.3 linkuse as main transcript	c.424G>A	p.Val142Met	missense_variant	3/3	ENST00000328739.6	NP_872372.1
VMO1	NM_001144939.2 linkuse as main transcript	c.*115G>A		3_prime_UTR_variant	3/3		NP_001138411.1
VMO1	NM_001144940.2 linkuse as main transcript	c.*95G>A		3_prime_UTR_variant	3/3		NP_001138412.1
VMO1	NM_001144941.2 linkuse as main transcript	c.*95G>A		3_prime_UTR_variant	2/2		NP_001138413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VMO1	ENST00000328739.6 linkuse as main transcript	c.424G>A	p.Val142Met	missense_variant	3/3	1	NM_182566.3	ENSP00000328397	P1	Q7Z5L0-1
VMO1	ENST00000354194.4 linkuse as main transcript	c.*95G>A		3_prime_UTR_variant	2/2	1		ENSP00000346133		Q7Z5L0-2
VMO1	ENST00000416307.6 linkuse as main transcript	c.*95G>A		3_prime_UTR_variant	3/3	2		ENSP00000390450		Q7Z5L0-3
VMO1	ENST00000441199.2 linkuse as main transcript	c.*115G>A		3_prime_UTR_variant	3/3	2		ENSP00000408166		Q7Z5L0-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727216

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:

8.99e-7

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

Nov 09, 2023

The c.424G>A (p.V142M) alteration is located in exon 3 (coding exon 3) of the VMO1 gene. This alteration results from a G to A substitution at nucleotide position 424, causing the valine (V) at amino acid position 142 to be replaced by a methionine (M). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.76

M_CAP

Benign

0.054

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.73

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

0.79

D;D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.30

Sift

Benign

0.030

Sift4G

Uncertain

0.0050

Polyphen

0.99

Vest4

0.44

MutPred

0.61

Loss of sheet (P = 0.0817);

MVP

0.30

MPC

1.3

ClinPred

0.93

GERP RS

4.0

Varity_R

0.16

gMVP

0.65

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

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