NM_007106.4:c.59A>G

Variant names:

• chr13-29777232-T-C
• rs1877023216
• NM_007106.4:c.59A>G

Variant summary

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

The NM_007106.4(UBL3):​c.59A>G​(p.Lys20Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,458,014 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: UBL3 NM_007106.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.40

Genes affected

UBL3 (HGNC:12504): (ubiquitin like 3) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBL3	NM_007106.4	c.59A>G	p.Lys20Arg	missense_variant	Exon 2 of 5	ENST00000380680.5	NP_009037.1
UBL3	XM_047430394.1	c.35A>G	p.Lys12Arg	missense_variant	Exon 3 of 6		XP_047286350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBL3	ENST00000380680.5	c.59A>G	p.Lys20Arg	missense_variant	Exon 2 of 5	1	NM_007106.4	ENSP00000370055.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1458014 Hom.: 0 Cov.: 30 AF XY: 0.0000262 AC XY: 19 AN XY: 724994

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: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000333

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.59A>G (p.K20R) alteration is located in exon 2 (coding exon 2) of the UBL3 gene. This alteration results from a A to G substitution at nucleotide position 59, causing the lysine (K) at amino acid position 20 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.073	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0088	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.45
Sift	Benign	0.12	T
Sift4G	Uncertain	0.033	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.40		Loss of ubiquitination at K20 (P = 0.0255);
MVP		0.51
MPC		1.3
ClinPred		0.95	D
GERP RS		5.8
Varity_R		0.26
gMVP		0.57

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: rs1877023216; hg19: chr13-30351369;