Variant chr4-75806549-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_003715.4(USO1):c.2353G>A(p.Glu785Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000107 in 1,405,680 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

USO1
NM_003715.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.19

Variant links:

Genes affected

USO1 (HGNC:30904): (USO1 vesicle transport factor) The protein encoded by this gene is a peripheral membrane protein which recycles between the cytosol and the Golgi apparatus during interphase. It is regulated by phosphorylation: dephosphorylated protein associates with the Golgi membrane and dissociates from the membrane upon phosphorylation. Ras-associated protein 1 recruits this protein to coat protein complex II (COPII) vesicles during budding from the endoplasmic reticulum, where it interacts with a set of COPII vesicle-associated SNAREs to form a cis-SNARE complex that promotes targeting to the Golgi apparatus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

USO1 links:

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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=0.17212111).

BP6

Variant 4-75806549-G-A is Benign according to our data. Variant chr4-75806549-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3055089.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
USO1	NM_003715.4 linkuse as main transcript	c.2353G>A	p.Glu785Lys	missense_variant	20/24	ENST00000514213.7
USO1	NM_001290049.2 linkuse as main transcript	c.2386G>A	p.Glu796Lys	missense_variant	22/26
USO1	XM_006714396.5 linkuse as main transcript	c.2374G>A	p.Glu792Lys	missense_variant	21/25
USO1	XM_006714397.4 linkuse as main transcript	c.2365G>A	p.Glu789Lys	missense_variant	21/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USO1	ENST00000514213.7 linkuse as main transcript	c.2353G>A	p.Glu785Lys	missense_variant	20/24	1	NM_003715.4	P3	O60763-1
USO1	ENST00000264904.8 linkuse as main transcript	c.2386G>A	p.Glu796Lys	missense_variant	22/26	2		A2	O60763-2
USO1	ENST00000508454.1 linkuse as main transcript	n.359G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000107

AC:

AN:

1405680

Hom.:

Cov.:

AF XY:

0.0000159

AC XY:

AN XY:

693854

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:

0.0000139

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

USO1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 01, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.55

REVEL

Benign

0.12

Sift4G

Benign

0.18

T;T

Polyphen

0.039

B;.

Vest4

0.37

MVP

0.082

ClinPred

0.54

GERP RS

4.2

Varity_R

0.083

gMVP

0.19

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