NM_001391956.1:c.4731G>T

Variant names:

• chr10-73498953-C-A
• rs371740699
• NM_001391956.1:c.4731G>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.4731G>T​(p.Lys1577Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,976 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (1 hom.)
• Consequence: USP54 NM_001391956.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.226
• Publications: 1 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=0.049680024).

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.4731G>T	p.Lys1577Asn	missense	Exon 24 of 24	NP_001378885.1	Q70EL1-1
	USP54	NM_001391941.1		c.4797G>T	p.Lys1599Asn	missense	Exon 24 of 24	NP_001378870.1
	USP54	NM_001391953.1		c.4731G>T	p.Lys1577Asn	missense	Exon 24 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.4731G>T	p.Lys1577Asn	missense	Exon 24 of 24	ENSP00000510226.1	Q70EL1-1
	USP54	ENST00000422491.7	TSL:1	c.*1696G>T		3_prime_UTR	Exon 20 of 20	ENSP00000407368.4	A0A804D9U3
	PPP3CB-AS1	ENST00000422977.3	TSL:1	n.1206-642C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152086 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251480 AF XY: 0.00000736

Gnomad AFR exome AF: 0.000123

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461890 Hom.: 1 Cov.: 34 AF XY: 0.0000124 AC XY: 9 AN XY: 727246

African (AFR) AF: 0.000299 AC: 10 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: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.0000497 AC: 3 AN: 60396

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152086 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74266

African (AFR) AF: 0.0000242 AC: 1 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000131 Hom.: 0

Bravo AF: 0.0000529

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

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	0.15
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.23
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.017
Sift	Benign	0.23	T
Sift4G	Benign	0.33	T
Polyphen		0.012	B
Vest4		0.078
MutPred		0.19		Loss of ubiquitination at K1577 (P = 0.0098)
MVP		0.15
MPC		0.20
ClinPred		0.068	T
GERP RS		3.0
Varity_R		0.060
gMVP		0.14
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: rs371740699; hg19: chr10-75258711;