chr3-132660541-G-A

Variant names:

• chr3-132660541-G-A
• rs1434532239
• NM_024818.6:c.4G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_024818.6(UBA5):​c.4G>A​(p.Ala2Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000931 in 1,396,526 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: UBA5 NM_024818.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.35216904).

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.4G>A	p.Ala2Thr	missense	Exon 1 of 12	NP_079094.1	Q9GZZ9-1
	UBA5	NM_001320210.2		c.-515G>A		5_prime_UTR	Exon 1 of 12	NP_001307139.1	Q9GZZ9-2
	UBA5	NM_001321238.2		c.-481G>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.4G>A	p.Ala2Thr	missense	Exon 1 of 12	ENSP00000348565.4	Q9GZZ9-1
	UBA5	ENST00000494238.6	TSL:1	c.-515G>A		5_prime_UTR	Exon 1 of 12	ENSP00000418807.2	Q9GZZ9-2
	NPHP3-ACAD11	ENST00000632629.1	TSL:2	c.636-15645C>T		intron	N/A	ENSP00000488520.1	A0A0J9YXS1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000655 AC: 1 AN: 152662 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.0000172

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000931 AC: 13 AN: 1396526 Hom.: 0 Cov.: 31 AF XY: 0.0000116 AC XY: 8 AN XY: 688830

African (AFR) AF: 0.0000317 AC: 1 AN: 31556

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25156

East Asian (EAS) AF: 0.00 AC: 0 AN: 35754

South Asian (SAS) AF: 0.00 AC: 0 AN: 79156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4282

European-Non Finnish (NFE) AF: 0.00000834 AC: 9 AN: 1078928

Other (OTH) AF: 0.0000519 AC: 3 AN: 57826

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.0010
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.81	T
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.8
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.020	N
REVEL	Uncertain	0.30
Sift	Benign	0.16	T
Sift4G	Benign	0.36	T
Polyphen		0.0010	B
Vest4		0.31
MutPred		0.17		Gain of glycosylation at S4 (P = 0.0012)
MVP		0.57
MPC		0.22
ClinPred		0.80	D
GERP RS		4.8
PromoterAI		-0.24	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.095
gMVP		0.50
Mutation Taster		=274/26	polymorphism

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: rs1434532239; hg19: chr3-132379385;