rs1378807

Variant names:

• chr3-132666346-C-G
• rs1378807
• NM_024818.6:c.297+273C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024818.6(UBA5):​c.297+273C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,952 control chromosomes in the GnomAD database, including 16,024 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 0.41 (16024 hom., cov: 33)
• Consequence: UBA5 NM_024818.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277
• Publications: 0 publications found

Genes affected

UBA5 (HGNC:23230): (ubiquitin like modifier activating enzyme 5) This gene encodes a member of the E1-like ubiquitin-activating enzyme family. This protein activates ubiquitin-fold modifier 1, a ubiquitin-like post-translational modifier protein, via the formation of a high-energy thioester bond. Alternative splicing results in multiple transcript variants. A pseudogene of this gene has been identified on chromosome 1. [provided by RefSeq, Feb 2016]

NPHP3-ACAD11 (HGNC:48351): (NPHP3-ACAD11 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring NPHP3 (nephronophthisis 3, adolescent) and ACAD11 (acyl-CoA dehydrogenase family, member 11) genes on chromosome 3. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024818.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBA5	NM_024818.6	MANE Select	c.297+273C>G		intron	N/A	NP_079094.1
	UBA5	NM_001320210.2		c.129+273C>G		intron	N/A	NP_001307139.1
	UBA5	NM_198329.4		c.129+273C>G		intron	N/A	NP_938143.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBA5	ENST00000356232.10	TSL:1 MANE Select	c.297+273C>G		intron	N/A	ENSP00000348565.4
	UBA5	ENST00000494238.6	TSL:1	c.129+273C>G		intron	N/A	ENSP00000418807.2
	NPHP3-ACAD11	ENST00000632629.1	TSL:2	c.635+15568G>C		intron	N/A	ENSP00000488520.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62822 AN: 151832 Hom.: 15988 Cov.: 33

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.414 AC: 62908 AN: 151952 Hom.: 16024 Cov.: 33 AF XY: 0.417 AC XY: 30990 AN XY: 74276

African (AFR) AF: 0.697 AC: 28908 AN: 41480

American (AMR) AF: 0.301 AC: 4592 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 863 AN: 3472

East Asian (EAS) AF: 0.763 AC: 3948 AN: 5174

South Asian (SAS) AF: 0.404 AC: 1945 AN: 4818

European-Finnish (FIN) AF: 0.335 AC: 3541 AN: 10556

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18052 AN: 67884

Other (OTH) AF: 0.388 AC: 817 AN: 2108

Alfa AF: 0.342 Hom.: 1377

Bravo AF: 0.424

Asia WGS AF: 0.535 AC: 1857 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.54
PhyloP100		-0.28
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: rs1378807; hg19: chr3-132385190;