chr20-3115331-G-A

Variant names:

• chr20-3115331-G-A
• rs1372502364
• NM_014948.4:c.1391C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014948.4(UBOX5):​c.1391C>T​(p.Thr464Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T464N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBOX5 NM_014948.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.119062096).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014948.4. 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
	UBOX5	NM_014948.4	MANE Select	c.1391C>T	p.Thr464Ile	missense	Exon 4 of 5	NP_055763.1	O94941-1
	UBOX5	NM_001267584.2		c.1391C>T	p.Thr464Ile	missense	Exon 4 of 5	NP_001254513.1
	UBOX5	NM_199415.3		c.1256-5017C>T		intron	N/A	NP_955447.1	O94941-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBOX5	ENST00000217173.7	TSL:1 MANE Select	c.1391C>T	p.Thr464Ile	missense	Exon 4 of 5	ENSP00000217173.2	O94941-1
	UBOX5	ENST00000348031.6	TSL:1	c.1256-5017C>T		intron	N/A	ENSP00000311726.3	O94941-2
	UBOX5	ENST00000896614.1		c.1391C>T	p.Thr464Ile	missense	Exon 3 of 4	ENSP00000566673.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.0
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.094
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.032	D
Polyphen		0.26	B
Vest4		0.18
MutPred		0.25		Loss of helix (P = 0.028)
MVP		0.52
MPC		0.29
ClinPred		0.53	D
GERP RS		4.0
Varity_R		0.17
gMVP		0.27
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1372502364; hg19: chr20-3095977;