chr4-75806549-G-A

Position:

• chr4-75806549-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.19

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 (HGNC:):

ACMG classification

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	Protein	UniProt
USO1	NM_003715.4	c.2353G>A	p.Glu785Lys	missense_variant	20/24	ENST00000514213.7	NP_003706.2
USO1	NM_001290049.2	c.2386G>A	p.Glu796Lys	missense_variant	22/26		NP_001276978.1
USO1	XM_006714396.5	c.2374G>A	p.Glu792Lys	missense_variant	21/25		XP_006714459.1
USO1	XM_006714397.4	c.2365G>A	p.Glu789Lys	missense_variant	21/25		XP_006714460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USO1	ENST00000514213.7	c.2353G>A	p.Glu785Lys	missense_variant	20/24	1	NM_003715.4	ENSP00000444850.2
USO1	ENST00000264904.8	c.2386G>A	p.Glu796Lys	missense_variant	22/26	2		ENSP00000264904.7
USO1	ENST00000508454.1	n.359G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000107 AC: 15 AN: 1405680 Hom.: 0 Cov.: 31 AF XY: 0.0000159 AC XY: 11 AN XY: 693854

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.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.55	T
REVEL	Benign	0.12
Sift4G	Benign	0.18	T;T
Polyphen		0.039	B;.
Vest4		0.37
MVP		0.082
ClinPred		0.54	D
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

Other links and lift over

dbSNP: rs1723002439; hg19: chr4-76727702;