NM_001391956.1:c.4292C>T

Variant names:

• chr10-73504869-G-A
• rs769214090
• NM_001391956.1:c.4292C>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.4292C>T​(p.Pro1431Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,614,124 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 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: USP54 NM_001391956.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27
• Publications: 2 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=0.041299254).

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.4292C>T	p.Pro1431Leu	missense	Exon 22 of 24	NP_001378885.1	Q70EL1-1
	USP54	NM_001391941.1		c.4358C>T	p.Pro1453Leu	missense	Exon 22 of 24	NP_001378870.1
	USP54	NM_001391953.1		c.4292C>T	p.Pro1431Leu	missense	Exon 22 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.4292C>T	p.Pro1431Leu	missense	Exon 22 of 24	ENSP00000510226.1	Q70EL1-1
	USP54	ENST00000422491.7	TSL:1	c.*1460+439C>T		intron	N/A	ENSP00000407368.4	A0A804D9U3
	PPP3CB-AS1	ENST00000422977.3	TSL:1	n.1719G>A		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251464 AF XY: 0.0000368

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: 0.0000703

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000445 AC: 65 AN: 1461894 Hom.: 0 Cov.: 30 AF XY: 0.0000440 AC XY: 32 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.0000486 AC: 54 AN: 1112012

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74428

African (AFR) AF: 0.00 AC: 0 AN: 41540

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000675 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.066
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.00052	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.3
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.033
Sift	Benign	0.98	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.15
MVP		0.18
MPC		0.25
ClinPred		0.082	T
GERP RS		1.6
Varity_R		0.043
gMVP		0.22
Mutation Taster		=97/3	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: rs769214090; hg19: chr10-75264627; COSMIC: COSV104411082; COSMIC: COSV104411082;