Variant 17-4785609-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182566.3(VMO1):c.362T>C(p.Val121Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,613,114 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

VMO1
NM_182566.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.021645606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VMO1	NM_182566.3 linkuse as main transcript	c.362T>C	p.Val121Ala	missense_variant	3/3	ENST00000328739.6	NP_872372.1
VMO1	NM_001144939.2 linkuse as main transcript	c.*53T>C		3_prime_UTR_variant	3/3		NP_001138411.1
VMO1	NM_001144940.2 linkuse as main transcript	c.*33T>C		3_prime_UTR_variant	3/3		NP_001138412.1
VMO1	NM_001144941.2 linkuse as main transcript	c.*33T>C		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.362T>C	p.Val121Ala	missense_variant	3/3	1	NM_182566.3	ENSP00000328397	P1	Q7Z5L0-1
VMO1	ENST00000354194.4 linkuse as main transcript	c.*33T>C		3_prime_UTR_variant	2/2	1		ENSP00000346133		Q7Z5L0-2
VMO1	ENST00000416307.6 linkuse as main transcript	c.*33T>C		3_prime_UTR_variant	3/3	2		ENSP00000390450		Q7Z5L0-3
VMO1	ENST00000441199.2 linkuse as main transcript	c.*53T>C		3_prime_UTR_variant	3/3	2		ENSP00000408166		Q7Z5L0-4

Frequencies

GnomAD3 genomes

AF:

0.000282

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

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:

0.0000294

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000480

AC:

AN:

249766

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135232

show subpopulations

Gnomad AFR exome

AF:

0.000494

Gnomad AMR exome

AF:

0.0000289

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:

0.00000883

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1460758

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

726738

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000268

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:

0.00000989

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000282

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000502

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

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

Nov 18, 2023

The c.362T>C (p.V121A) alteration is located in exon 3 (coding exon 3) of the VMO1 gene. This alteration results from a T to C substitution at nucleotide position 362, causing the valine (V) at amino acid position 121 to be replaced by an alanine (A). 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

-0.36

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.010

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.52

M_CAP

Benign

0.015

MetaRNN

Benign

0.022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.70

D;D;D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.3

REVEL

Benign

0.095

Sift

Benign

0.23

Sift4G

Benign

0.34

Polyphen

0.029

Vest4

0.15

MVP

0.099

MPC

0.78

ClinPred

0.017

GERP RS

1.4

Varity_R

0.12

gMVP

0.45

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