rs1378807

Positions:

• chr3-132666346-C-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBA5	NM_024818.6	c.297+273C>G		intron_variant		ENST00000356232.10
NPHP3-ACAD11	NR_037804.1	n.3995+15568G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBA5	ENST00000356232.10	c.297+273C>G		intron_variant		1	NM_024818.6	P1

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

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.388

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.54

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: rs1378807; hg19: chr3-132385190;