NM_001391956.1:c.4351C>T

Variant names:

• chr10-73500799-G-A
• rs138141992
• NM_001391956.1:c.4351C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001391956.1(USP54):​c.4351C>T​(p.Arg1451Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000247 in 1,599,168 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: USP54 NM_001391956.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 5.62
• Publications: 3 publications found

Genes affected

USP54 (HGNC:23513): (ubiquitin specific peptidase 54) Predicted to enable thiol-dependent deubiquitinase. Predicted to be involved in protein deubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

PPP3CB-AS1 (HGNC:50750): (PPP3CB antisense RNA 1 (head to head))

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00769186).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001391956.1. 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
	USP54	NM_001391956.1	MANE Select	c.4351C>T	p.Arg1451Cys	missense	Exon 23 of 24	NP_001378885.1	Q70EL1-1
	USP54	NM_001391941.1		c.4417C>T	p.Arg1473Cys	missense	Exon 23 of 24	NP_001378870.1
	USP54	NM_001391953.1		c.4351C>T	p.Arg1451Cys	missense	Exon 23 of 24	NP_001378882.1	Q70EL1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP54	ENST00000687698.1	MANE Select	c.4351C>T	p.Arg1451Cys	missense	Exon 23 of 24	ENSP00000510226.1	Q70EL1-1
	USP54	ENST00000422491.7	TSL:1	c.*1461-1611C>T		intron	N/A	ENSP00000407368.4	A0A804D9U3
	PPP3CB-AS1	ENST00000422977.3	TSL:1	n.1298+1112G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 205 AN: 152100 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00435

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000379 AC: 89 AN: 234592 AF XY: 0.000352

Gnomad AFR exome AF: 0.00392

Gnomad AMR exome AF: 0.000267

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000607

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000278

Gnomad OTH exome AF: 0.000177

GnomAD4 exome AF: 0.000130 AC: 188 AN: 1446950 Hom.: 1 Cov.: 31 AF XY: 0.000131 AC XY: 94 AN XY: 720138

African (AFR) AF: 0.00304 AC: 98 AN: 32212

American (AMR) AF: 0.000247 AC: 10 AN: 40528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25570

East Asian (EAS) AF: 0.0000778 AC: 3 AN: 38536

South Asian (SAS) AF: 0.000569 AC: 48 AN: 84336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.0000136 AC: 15 AN: 1107000

Other (OTH) AF: 0.000234 AC: 14 AN: 59776

GnomAD4 genome AF: 0.00136 AC: 207 AN: 152218 Hom.: 0 Cov.: 32 AF XY: 0.00137 AC XY: 102 AN XY: 74422

African (AFR) AF: 0.00438 AC: 182 AN: 41524

American (AMR) AF: 0.000915 AC: 14 AN: 15298

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.000479 Hom.: 0

Bravo AF: 0.00114

ESP6500AA AF: 0.00318 AC: 14

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000428 AC: 52

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)
-	-	1	USP54-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.040	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.0077	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.6
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.13
Sift	Benign	0.079	T
Sift4G	Uncertain	0.011	D
Polyphen		0.20	B
Vest4		0.43
MVP		0.32
MPC		0.72
ClinPred		0.063	T
GERP RS		5.3
Varity_R		0.16
gMVP		0.29
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs138141992; hg19: chr10-75260557;