rs34606078

Variant names:

• chr20-3110238-C-A
• rs34606078
• NM_014948.4:c.1494G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-3110238-C-A
• chr20-3110238-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001267584.2(UBOX5):​c.1489G>T​(p.Gly497Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,614,068 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (17 hom., cov: 33)
  • Exomes 𝑓: 0.014 (147 hom.)
• Consequence: UBOX5 NM_001267584.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.36
• Publications: 6 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 20-3110238-C-A is Benign according to our data. Variant chr20-3110238-C-A is described in ClinVar as Benign. ClinVar VariationId is 3024835.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001267584.2. 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.1494G>T	p.Pro498Pro	synonymous	Exon 5 of 5	NP_055763.1	O94941-1
	UBOX5	NM_001267584.2		c.1489G>T	p.Gly497Cys	missense	Exon 5 of 5	NP_001254513.1
	UBOX5	NM_199415.3		c.1332G>T	p.Pro444Pro	synonymous	Exon 4 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.1494G>T	p.Pro498Pro	synonymous	Exon 5 of 5	ENSP00000217173.2	O94941-1
	UBOX5	ENST00000348031.6	TSL:1	c.1332G>T	p.Pro444Pro	synonymous	Exon 4 of 4	ENSP00000311726.3	O94941-2
	UBOX5	ENST00000896614.1		c.1494G>T	p.Pro498Pro	synonymous	Exon 4 of 4	ENSP00000566673.1

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1823 AN: 152176 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.00299

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0330

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.0124 AC: 3114 AN: 251458 AF XY: 0.0125

Gnomad AFR exome AF: 0.00160

Gnomad AMR exome AF: 0.00457

Gnomad ASJ exome AF: 0.0152

Gnomad EAS exome AF: 0.00190

Gnomad FIN exome AF: 0.0287

Gnomad NFE exome AF: 0.0148

Gnomad OTH exome AF: 0.0109

GnomAD4 exome AF: 0.0136 AC: 19863 AN: 1461774 Hom.: 147 Cov.: 33 AF XY: 0.0136 AC XY: 9867 AN XY: 727174

African (AFR) AF: 0.00200 AC: 67 AN: 33476

American (AMR) AF: 0.00458 AC: 205 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0142 AC: 371 AN: 26136

East Asian (EAS) AF: 0.00214 AC: 85 AN: 39700

South Asian (SAS) AF: 0.0127 AC: 1098 AN: 86252

European-Finnish (FIN) AF: 0.0266 AC: 1423 AN: 53416

Middle Eastern (MID) AF: 0.00492 AC: 28 AN: 5696

European-Non Finnish (NFE) AF: 0.0143 AC: 15933 AN: 1111992

Other (OTH) AF: 0.0108 AC: 653 AN: 60382

GnomAD4 genome AF: 0.0120 AC: 1824 AN: 152294 Hom.: 17 Cov.: 33 AF XY: 0.0129 AC XY: 964 AN XY: 74468

African (AFR) AF: 0.00298 AC: 124 AN: 41570

American (AMR) AF: 0.0114 AC: 174 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3470

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5182

South Asian (SAS) AF: 0.0122 AC: 59 AN: 4822

European-Finnish (FIN) AF: 0.0330 AC: 350 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0151 AC: 1030 AN: 68022

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.0121 Hom.: 26

Bravo AF: 0.00976

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0116

EpiControl AF: 0.0133

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.094
DANN	Benign	0.85
PhyloP100		-4.4
Mutation Taster		=99/1	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: rs34606078; hg19: chr20-3090884;