20-3121676-G-T

Position:

• chr20-3121676-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014948.4(UBOX5):​c.963C>A​(p.His321Gln) 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. 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: 3.18

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37210292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBOX5	NM_014948.4	c.963C>A	p.His321Gln	missense_variant	3/5	ENST00000217173.7	NP_055763.1
UBOX5-AS1	NR_038395.1	n.1308+9924G>T		intron_variant, non_coding_transcript_variant
UBOX5	NM_001267584.2	c.963C>A	p.His321Gln	missense_variant	3/5		NP_001254513.1
UBOX5	NM_199415.3	c.963C>A	p.His321Gln	missense_variant	3/4		NP_955447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBOX5	ENST00000217173.7	c.963C>A	p.His321Gln	missense_variant	3/5	1	NM_014948.4	ENSP00000217173	P1
UBOX5	ENST00000348031.6	c.963C>A	p.His321Gln	missense_variant	3/4	1		ENSP00000311726
UBOX5-AS1	ENST00000446537.5	n.1306+9924G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2022

The c.963C>A (p.H321Q) 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 963, causing the histidine (H) at amino acid position 321 to be replaced by a glutamine (Q). 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	Pathogenic	0.69
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	D;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.51	N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.18
Sift	Benign	0.084	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.85	P;.
Vest4		0.58
MutPred		0.66		Gain of ubiquitination at K325 (P = 0.1215);Gain of ubiquitination at K325 (P = 0.1215);
MVP		0.55
MPC		0.53
ClinPred		0.89	D
GERP RS		3.4
Varity_R		0.24
gMVP		0.74

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: chr20-3102322;