20-3121627-G-C

Variant names:

• chr20-3121627-G-C
• rs766981340
• NM_014948.4:c.1012C>G

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.1012C>G​(p.Pro338Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P338S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: UBOX5 NM_014948.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.95
• 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=0.22372016).

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.1012C>G	p.Pro338Ala	missense	Exon 3 of 5	NP_055763.1	O94941-1
	UBOX5	NM_001267584.2		c.1012C>G	p.Pro338Ala	missense	Exon 3 of 5	NP_001254513.1
	UBOX5	NM_199415.3		c.1012C>G	p.Pro338Ala	missense	Exon 3 of 4	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.1012C>G	p.Pro338Ala	missense	Exon 3 of 5	ENSP00000217173.2	O94941-1
	UBOX5	ENST00000348031.6	TSL:1	c.1012C>G	p.Pro338Ala	missense	Exon 3 of 4	ENSP00000311726.3	O94941-2
	UBOX5	ENST00000896614.1		c.1012C>G	p.Pro338Ala	missense	Exon 2 of 4	ENSP00000566673.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458694 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725410

African (AFR) AF: 0.00 AC: 0 AN: 33386

American (AMR) AF: 0.00 AC: 0 AN: 44222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39548

South Asian (SAS) AF: 0.00 AC: 0 AN: 85744

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110554

Other (OTH) AF: 0.00 AC: 0 AN: 60274

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.0
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.064
Sift	Benign	0.051	T
Sift4G	Benign	0.18	T
Polyphen		0.93	P
Vest4		0.29
MutPred		0.49		Gain of catalytic residue at P338 (P = 0.0135)
MVP		0.56
MPC		0.28
ClinPred		0.34	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.039
gMVP		0.17
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs766981340; hg19: chr20-3102273;