chr3-69076730-A-C

Variant names:

• chr3-69076730-A-C
• rs3853154
• NM_003968.4:c.183+1068T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
UBA3	NM_003968.4	c.183+1068T>G		intron_variant	Intron 3 of 17	ENST00000361055.9	NP_003959.3
UBA3	NM_198195.2	c.141+1068T>G		intron_variant	Intron 2 of 16		NP_937838.1
UBA3	NM_001363861.1	c.141+1068T>G		intron_variant	Intron 2 of 15		NP_001350790.1
UBA3	XM_011534210.2	c.183+1068T>G		intron_variant	Intron 3 of 16		XP_011532512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBA3	ENST00000361055.9	c.183+1068T>G		intron_variant	Intron 3 of 17	1	NM_003968.4	ENSP00000354340.4

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

African (AFR) AF: 0.598 AC: 24640 AN: 41208

American (AMR) AF: 0.505 AC: 7681 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2197 AN: 3464

East Asian (EAS) AF: 0.820 AC: 4221 AN: 5146

South Asian (SAS) AF: 0.660 AC: 3154 AN: 4778

European-Finnish (FIN) AF: 0.596 AC: 6126 AN: 10286

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 38880 AN: 67750

Other (OTH) AF: 0.596 AC: 1252 AN: 2100

Alfa AF: 0.582 Hom.: 20936

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
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3853154; hg19: chr3-69125881;