rs376891080

Variant names:

• chr3-132660558-C-T
• rs376891080
• NM_024818.6:c.21C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS1

The NM_024818.6(UBA5):​c.21C>T​(p.Arg7Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,549,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: UBA5 NM_024818.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.58
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 3-132660558-C-T is Benign according to our data. Variant chr3-132660558-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1628906.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.58 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000985 (15/152278) while in subpopulation AFR AF = 0.000337 (14/41552). AF 95% confidence interval is 0.000204. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.21C>T	p.Arg7Arg	synonymous	Exon 1 of 12	NP_079094.1	Q9GZZ9-1
	UBA5	NM_001320210.2		c.-498C>T		5_prime_UTR	Exon 1 of 12	NP_001307139.1	Q9GZZ9-2
	UBA5	NM_001321238.2		c.-464C>T		5_prime_UTR	Exon 1 of 10	NP_001308167.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBA5	ENST00000356232.10	TSL:1 MANE Select	c.21C>T	p.Arg7Arg	synonymous	Exon 1 of 12	ENSP00000348565.4	Q9GZZ9-1
	UBA5	ENST00000494238.6	TSL:1	c.-498C>T		5_prime_UTR	Exon 1 of 12	ENSP00000418807.2	Q9GZZ9-2
	NPHP3-ACAD11	ENST00000632629.1	TSL:2	c.636-15662G>A		intron	N/A	ENSP00000488520.1	A0A0J9YXS1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000646 AC: 1 AN: 154860 AF XY: 0.00

Gnomad AFR exome AF: 0.000119

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000501 AC: 7 AN: 1397486 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 2 AN XY: 689344

African (AFR) AF: 0.000222 AC: 7 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25162

East Asian (EAS) AF: 0.00 AC: 0 AN: 35802

South Asian (SAS) AF: 0.00 AC: 0 AN: 79182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4472

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079198

Other (OTH) AF: 0.00 AC: 0 AN: 57880

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152278 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74454

African (AFR) AF: 0.000337 AC: 14 AN: 41552

American (AMR) AF: 0.0000654 AC: 1 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000982

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	14
DANN	Uncertain	0.98
PhyloP100		2.6
PromoterAI		0.023	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6

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: rs376891080; hg19: chr3-132379402;