NM_014948.4:c.1052C>T

Variant names:

• chr20-3121587-G-A
• rs746442167
• NM_014948.4:c.1052C>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.1052C>T​(p.Ala351Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000573 in 1,604,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000061 (0 hom.)
• Consequence: UBOX5 NM_014948.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.07
• 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=0.08201873).

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.1052C>T	p.Ala351Val	missense	Exon 3 of 5	NP_055763.1	O94941-1
	UBOX5	NM_001267584.2		c.1052C>T	p.Ala351Val	missense	Exon 3 of 5	NP_001254513.1
	UBOX5	NM_199415.3		c.1052C>T	p.Ala351Val	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.1052C>T	p.Ala351Val	missense	Exon 3 of 5	ENSP00000217173.2	O94941-1
	UBOX5	ENST00000348031.6	TSL:1	c.1052C>T	p.Ala351Val	missense	Exon 3 of 4	ENSP00000311726.3	O94941-2
	UBOX5	ENST00000896614.1		c.1052C>T	p.Ala351Val	missense	Exon 2 of 4	ENSP00000566673.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152018 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000303 AC: 7 AN: 230978 AF XY: 0.0000321

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000584

Gnomad OTH exome AF: 0.000175

GnomAD4 exome AF: 0.0000606 AC: 88 AN: 1452512 Hom.: 0 Cov.: 31 AF XY: 0.0000707 AC XY: 51 AN XY: 721838

African (AFR) AF: 0.00 AC: 0 AN: 33246

American (AMR) AF: 0.0000234 AC: 1 AN: 42718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25868

East Asian (EAS) AF: 0.00 AC: 0 AN: 39298

South Asian (SAS) AF: 0.00 AC: 0 AN: 85182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52934

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5760

European-Non Finnish (NFE) AF: 0.0000749 AC: 83 AN: 1107452

Other (OTH) AF: 0.0000500 AC: 3 AN: 60054

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152018 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74242

African (AFR) AF: 0.00 AC: 0 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000581 Hom.: 0

Bravo AF: 0.0000227

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.1
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.059
Sift	Benign	0.37	T
Sift4G	Benign	0.53	T
Polyphen		0.0060	B
Vest4		0.069
MVP		0.44
MPC		0.27
ClinPred		0.052	T
GERP RS		4.3
Varity_R		0.024
gMVP		0.23
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs746442167; hg19: chr20-3102233; COSMIC: COSV53907028; COSMIC: COSV53907028;