3-69076730-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003968.4(UBA3):​c.183+1068T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBA3	NM_003968.4	c.183+1068T>C		intron_variant	Intron 3 of 17	ENST00000361055.9	NP_003959.3
UBA3	NM_198195.2	c.141+1068T>C		intron_variant	Intron 2 of 16		NP_937838.1
UBA3	NM_001363861.1	c.141+1068T>C		intron_variant	Intron 2 of 15		NP_001350790.1
UBA3	XM_011534210.2	c.183+1068T>C		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>C		intron_variant	Intron 3 of 17	1	NM_003968.4	ENSP00000354340.4

Frequencies

GnomAD3 genomes Cov.: 29

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

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.82
PhyloP100		-0.64

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;