NM_001391956.1:c.4880G>C

Variant names:

• chr10-73498804-C-G
• rs754158099
• NM_001391956.1:c.4880G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001391956.1(USP54):​c.4880G>C​(p.Arg1627Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1627Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: USP54 NM_001391956.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26223907).

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.4880G>C	p.Arg1627Pro	missense	Exon 24 of 24	NP_001378885.1	Q70EL1-1
	USP54	NM_001391941.1		c.4946G>C	p.Arg1649Pro	missense	Exon 24 of 24	NP_001378870.1
	USP54	NM_001391953.1		c.4880G>C	p.Arg1627Pro	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.4880G>C	p.Arg1627Pro	missense	Exon 24 of 24	ENSP00000510226.1	Q70EL1-1
	USP54	ENST00000422491.7	TSL:1	c.*1845G>C		3_prime_UTR	Exon 20 of 20	ENSP00000407368.4	A0A804D9U3
	PPP3CB-AS1	ENST00000422977.3	TSL:1	n.1206-791C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250242 AF XY: 0.00000739

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: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434214 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 712986

African (AFR) AF: 0.00 AC: 0 AN: 32786

American (AMR) AF: 0.00 AC: 0 AN: 43774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25128

East Asian (EAS) AF: 0.00 AC: 0 AN: 37792

South Asian (SAS) AF: 0.00 AC: 0 AN: 85854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5620

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1094138

Other (OTH) AF: 0.00 AC: 0 AN: 58608

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0058	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.036
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.5
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.024	D
Polyphen		0.94	P
Vest4		0.50
MutPred		0.14		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.39
MPC		0.58
ClinPred		0.74	D
GERP RS		4.3
Varity_R		0.24
gMVP		0.38
Mutation Taster		=81/19	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: rs754158099; hg19: chr10-75258562;