NM_024818.6:c.84G>A

Variant names:

• chr3-132660621-G-A
• rs1444209036
• NM_024818.6:c.84G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_024818.6(UBA5):​c.84G>A​(p.Pro28Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 1,562,288 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: UBA5 NM_024818.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.788
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-132660621-G-A is Benign according to our data. Variant chr3-132660621-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1952878.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.788 with no splicing effect.

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.84G>A	p.Pro28Pro	synonymous	Exon 1 of 12	NP_079094.1	Q9GZZ9-1
	UBA5	NM_001320210.2		c.-435G>A		5_prime_UTR	Exon 1 of 12	NP_001307139.1	Q9GZZ9-2
	UBA5	NM_001321238.2		c.-401G>A		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.84G>A	p.Pro28Pro	synonymous	Exon 1 of 12	ENSP00000348565.4	Q9GZZ9-1
	UBA5	ENST00000494238.6	TSL:1	c.-435G>A		5_prime_UTR	Exon 1 of 12	ENSP00000418807.2	Q9GZZ9-2
	NPHP3-ACAD11	ENST00000632629.1	TSL:2	c.636-15725C>T		intron	N/A	ENSP00000488520.1	A0A0J9YXS1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1410102 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 696550

African (AFR) AF: 0.0000311 AC: 1 AN: 32142

American (AMR) AF: 0.00 AC: 0 AN: 36796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25280

East Asian (EAS) AF: 0.00 AC: 0 AN: 36616

South Asian (SAS) AF: 0.00 AC: 0 AN: 79924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5468

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085694

Other (OTH) AF: 0.00 AC: 0 AN: 58472

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74350

African (AFR) AF: 0.0000241 AC: 1 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

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	-0.81
CADD	Benign	5.9
DANN	Benign	0.82
PhyloP100		0.79
PromoterAI		-0.0033	Neutral

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: rs1444209036; hg19: chr3-132379465;