rs3853154

chr3-69076730-A-Cchr3-69076730-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003968.4(UBA3):c.183+1068T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 151,138 control chromosomes in the GnomAD database, including 26,136 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (26136 hom., cov: 29)
• Consequence: UBA3 NM_003968.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643

Genes affected

UBA3 (HGNC:12470): (ubiquitin like modifier activating enzyme 3) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E1 ubiquitin-activating enzyme family. The encoded enzyme associates with AppBp1, an amyloid beta precursor protein binding protein, to form a heterodimer, and then the enzyme complex activates NEDD8, a ubiquitin-like protein, which regulates cell division, signaling and embryogenesis. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBA3	NM_003968.4	c.183+1068T>G		intron_variant		ENST00000361055.9
UBA3	NM_001363861.1	c.141+1068T>G		intron_variant
UBA3	NM_198195.2	c.141+1068T>G		intron_variant
UBA3	XM_011534210.2	c.183+1068T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBA3	ENST00000361055.9	c.183+1068T>G		intron_variant		1	NM_003968.4	P4

Frequencies

GnomAD3 genomes AF: 0.587 AC: 88703 AN: 151026 Hom.: 26108 Cov.: 29

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.602

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.587 AC: 88784 AN: 151138 Hom.: 26136 Cov.: 29 AF XY: 0.592 AC XY: 43700 AN XY: 73810

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.596

Alfa AF: 0.584 Hom.: 17875

Bravo AF: 0.582

Asia WGS AF: 0.666 AC: 2318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.94
Dann	Benign	0.49

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: rs3853154; hg19: chr3-69125881;