20-3115311-C-T

Variant names:

• chr20-3115311-C-T
• rs753709017
• NM_014948.4:c.1411G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014948.4(UBOX5):​c.1411G>A​(p.Gly471Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000823 in 1,458,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 0.0000082 (0 hom.)
• Consequence: UBOX5 NM_014948.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.33

Genes affected

UBOX5 (HGNC:17777): (U-box domain containing 5) This gene encodes a U-box domain containing protein. The encoded protein interacts with E2 enzymes and may play a role in the ubiquitination pathway. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

UBOX5-AS1 (HGNC:44111): (UBOX5 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031015664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBOX5	NM_014948.4	c.1411G>A	p.Gly471Ser	missense_variant	Exon 4 of 5	ENST00000217173.7	NP_055763.1
UBOX5	NM_001267584.2	c.1411G>A	p.Gly471Ser	missense_variant	Exon 4 of 5		NP_001254513.1
UBOX5	NM_199415.3	c.1256-4997G>A		intron_variant	Intron 3 of 3		NP_955447.1
UBOX5-AS1	NR_038395.1	n.1308+3559C>T		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBOX5	ENST00000217173.7	c.1411G>A	p.Gly471Ser	missense_variant	Exon 4 of 5	1	NM_014948.4	ENSP00000217173.2
UBOX5	ENST00000348031.6	c.1256-4997G>A		intron_variant	Intron 3 of 3	1		ENSP00000311726.3
UBOX5-AS1	ENST00000446537.5	n.1306+3559C>T		intron_variant	Intron 5 of 6	2
UBOX5-AS1	ENST00000454019.1	n.191-1178C>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000811 AC: 2 AN: 246634 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133372

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad SAS 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: 0.00000823 AC: 12 AN: 1458452 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 725520

Gnomad4 AFR exome AF: 0.0000601

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000720

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000280 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 12, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.0
DANN	Benign	0.91
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.69	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.66	N
REVEL	Benign	0.049
Sift	Benign	0.58	T
Sift4G	Benign	0.82	T
Polyphen		0.0020	B
Vest4		0.099
MutPred		0.14		Gain of relative solvent accessibility (P = 0.0249);
MVP		0.20
MPC		0.26
ClinPred		0.022	T
GERP RS		-5.8
Varity_R		0.033
gMVP		0.18

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: rs753709017; hg19: chr20-3095957;