NM_001098536.2:c.1138C>T

Variant names:

• chr12-6860158-C-T
• rs76083908
• NM_001098536.2:c.1138C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001098536.2(USP5):​c.1138C>T​(p.Leu380Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00418 in 1,607,256 control chromosomes in the GnomAD database, including 243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (135 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (108 hom.)
• Consequence: USP5 NM_001098536.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.30
• 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 12-6860158-C-T is Benign according to our data. Variant chr12-6860158-C-T is described in ClinVar as Benign. ClinVar VariationId is 781061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.3 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

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.1138C>T	p.Leu380Leu	synonymous	Exon 10 of 20	NP_001092006.1	A0A140VJZ1
	USP5	NM_003481.3		c.1138C>T	p.Leu380Leu	synonymous	Exon 10 of 20	NP_003472.2	P45974-2
	USP5	NM_001382591.1		c.1066C>T	p.Leu356Leu	synonymous	Exon 9 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.1138C>T	p.Leu380Leu	synonymous	Exon 10 of 20	ENSP00000229268.8	P45974-1
	USP5	ENST00000389231.9	TSL:1	c.1138C>T	p.Leu380Leu	synonymous	Exon 10 of 20	ENSP00000373883.5	P45974-2
	USP5	ENST00000864808.1		c.1138C>T	p.Leu380Leu	synonymous	Exon 10 of 20	ENSP00000534867.1

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 3327 AN: 152192 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

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: 0.000191

Gnomad OTH AF: 0.0177

GnomAD2 exomes AF: 0.00566 AC: 1376 AN: 243316 AF XY: 0.00428

Gnomad AFR exome AF: 0.0766

Gnomad AMR exome AF: 0.00325

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000224

Gnomad OTH exome AF: 0.00253

GnomAD4 exome AF: 0.00232 AC: 3380 AN: 1454946 Hom.: 108 Cov.: 31 AF XY: 0.00204 AC XY: 1477 AN XY: 724004

African (AFR) AF: 0.0823 AC: 2700 AN: 32802

American (AMR) AF: 0.00349 AC: 147 AN: 42068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25858

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.0000939 AC: 8 AN: 85196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00402 AC: 23 AN: 5722

European-Non Finnish (NFE) AF: 0.000191 AC: 212 AN: 1110168

Other (OTH) AF: 0.00483 AC: 290 AN: 60096

GnomAD4 genome AF: 0.0219 AC: 3336 AN: 152310 Hom.: 135 Cov.: 32 AF XY: 0.0219 AC XY: 1628 AN XY: 74478

African (AFR) AF: 0.0763 AC: 3168 AN: 41546

American (AMR) AF: 0.00771 AC: 118 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68030

Other (OTH) AF: 0.0175 AC: 37 AN: 2114

Alfa AF: 0.0115 Hom.: 32

Bravo AF: 0.0238

Asia WGS AF: 0.00433 AC: 16 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000415

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	-0.31
CADD	Benign	11
DANN	Benign	0.74
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs76083908; hg19: chr12-6969322;