chr3-132660557-G-C

Variant names:

• chr3-132660557-G-C
• rs770749604
• NM_024818.6:c.20G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024818.6(UBA5):​c.20G>C​(p.Arg7Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,397,360 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: UBA5 NM_024818.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25193956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBA5	NM_024818.6	c.20G>C	p.Arg7Pro	missense_variant	Exon 1 of 12	ENST00000356232.10	NP_079094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBA5	ENST00000356232.10	c.20G>C	p.Arg7Pro	missense_variant	Exon 1 of 12	1	NM_024818.6	ENSP00000348565.4
NPHP3-ACAD11	ENST00000632629.1	c.636-15661C>G		intron_variant	Intron 4 of 4	2		ENSP00000488520.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000647 AC: 1 AN: 154558 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 81694

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 SAS exome AF: 0.0000439

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1397360 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689270

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.0090
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.80	T;T;T
M_CAP	Pathogenic	0.59	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.8	L;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.88	N;N;N
REVEL	Uncertain	0.48
Sift	Benign	0.082	T;T;T
Sift4G	Benign	0.098	T;T;T
Polyphen		0.39	B;.;B
Vest4		0.44
MutPred		0.32		Loss of MoRF binding (P = 0);Loss of MoRF binding (P = 0);Loss of MoRF binding (P = 0);
MVP		0.77
MPC		0.39
ClinPred		0.58	D
GERP RS		4.0
Varity_R		0.49
gMVP		0.51

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: rs770749604; hg19: chr3-132379401;