NM_001098536.2:c.54C>T

Variant names:

• chr12-6852233-C-T
• rs143249320
• NM_001098536.2:c.54C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001098536.2(USP5):​c.54C>T​(p.Val18Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,613,370 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0090 (26 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (27 hom.)
• Consequence: USP5 NM_001098536.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.175
• Publications: 2 publications found

Genes affected

USP5 (HGNC:12628): (ubiquitin specific peptidase 5) Ubiquitin (see MIM 191339)-dependent proteolysis is a complex pathway of protein metabolism implicated in such diverse cellular functions as maintenance of chromatin structure, receptor function, and degradation of abnormal proteins. A late step of the process involves disassembly of the polyubiquitin chains on degraded proteins into ubiquitin monomers. USP5 disassembles branched polyubiquitin chains by a sequential exo mechanism, starting at the proximal end of the chain (Wilkinson et al., 1995 [PubMed 7578059]).[supplied by OMIM, Mar 2010]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 12-6852233-C-T is Benign according to our data. Variant chr12-6852233-C-T is described in ClinVar as Benign. ClinVar VariationId is 783654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.175 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00903 (1376/152344) while in subpopulation AFR AF = 0.0314 (1306/41570). AF 95% confidence interval is 0.03. There are 26 homozygotes in GnomAd4. There are 642 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098536.2. 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
	USP5	NM_001098536.2	MANE Select	c.54C>T	p.Val18Val	synonymous	Exon 1 of 20	NP_001092006.1	A0A140VJZ1
	USP5	NM_003481.3		c.54C>T	p.Val18Val	synonymous	Exon 1 of 20	NP_003472.2	P45974-2
	USP5	NM_001382591.1		c.54C>T	p.Val18Val	synonymous	Exon 1 of 19	NP_001369520.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP5	ENST00000229268.13	TSL:1 MANE Select	c.54C>T	p.Val18Val	synonymous	Exon 1 of 20	ENSP00000229268.8	P45974-1
	USP5	ENST00000389231.9	TSL:1	c.54C>T	p.Val18Val	synonymous	Exon 1 of 20	ENSP00000373883.5	P45974-2
	USP5	ENST00000864808.1		c.54C>T	p.Val18Val	synonymous	Exon 1 of 20	ENSP00000534867.1

Frequencies

GnomAD3 genomes AF: 0.00906 AC: 1379 AN: 152226 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00235

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.00256 AC: 636 AN: 248324 AF XY: 0.00185

Gnomad AFR exome AF: 0.0350

Gnomad AMR exome AF: 0.00137

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000160

Gnomad OTH exome AF: 0.00166

GnomAD4 exome AF: 0.00106 AC: 1551 AN: 1461026 Hom.: 27 Cov.: 31 AF XY: 0.000930 AC XY: 676 AN XY: 726666

African (AFR) AF: 0.0343 AC: 1148 AN: 33470

American (AMR) AF: 0.00141 AC: 63 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.0000931 AC: 8 AN: 85922

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5766

European-Non Finnish (NFE) AF: 0.000162 AC: 180 AN: 1111766

Other (OTH) AF: 0.00219 AC: 132 AN: 60370

GnomAD4 genome AF: 0.00903 AC: 1376 AN: 152344 Hom.: 26 Cov.: 33 AF XY: 0.00862 AC XY: 642 AN XY: 74502

African (AFR) AF: 0.0314 AC: 1306 AN: 41570

American (AMR) AF: 0.00229 AC: 35 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68030

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

Alfa AF: 0.00524 Hom.: 3

Bravo AF: 0.0106

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.94
PhyloP100		0.17
PromoterAI		-0.036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=90/10	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: rs143249320; hg19: chr12-6961397;