NM_014948.4:c.940C>A

Variant names:

• chr20-3121699-G-T
• NM_014948.4:c.940C>A

Variant summary

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

The NM_014948.4(UBOX5):​c.940C>A​(p.Pro314Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBOX5 NM_014948.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65

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 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=0.14849359).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBOX5	NM_014948.4	c.940C>A	p.Pro314Thr	missense_variant	Exon 3 of 5	ENST00000217173.7	NP_055763.1
UBOX5	NM_001267584.2	c.940C>A	p.Pro314Thr	missense_variant	Exon 3 of 5		NP_001254513.1
UBOX5	NM_199415.3	c.940C>A	p.Pro314Thr	missense_variant	Exon 3 of 4		NP_955447.1
UBOX5-AS1	NR_038395.1	n.1308+9947G>T		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBOX5	ENST00000217173.7	c.940C>A	p.Pro314Thr	missense_variant	Exon 3 of 5	1	NM_014948.4	ENSP00000217173.2
UBOX5	ENST00000348031.6	c.940C>A	p.Pro314Thr	missense_variant	Exon 3 of 4	1		ENSP00000311726.3
UBOX5-AS1	ENST00000446537.5	n.1306+9947G>T		intron_variant	Intron 5 of 6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.940C>A (p.P314T) alteration is located in exon 3 (coding exon 2) of the UBOX5 gene. This alteration results from a C to A substitution at nucleotide position 940, causing the proline (P) at amino acid position 314 to be replaced by a threonine (T). 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	0.081
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.30	T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	T;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.82	N;N
REVEL	Benign	0.027
Sift	Benign	0.12	T;T
Sift4G	Benign	0.49	T;T
Polyphen		0.21	B;.
Vest4		0.17
MutPred		0.43		Gain of catalytic residue at P314 (P = 0.0197);Gain of catalytic residue at P314 (P = 0.0197);
MVP		0.49
MPC		0.35
ClinPred		0.21	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.063
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-3102345;