NM_001391956.1:c.4345G>A

Variant names:

• chr10-73500805-C-T
• rs111294104
• NM_001391956.1:c.4345G>A

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.4345G>A​(p.Gly1449Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,598,348 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 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: USP54 NM_001391956.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0130
• 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: 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=0.10037035).

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.4345G>A	p.Gly1449Arg	missense	Exon 23 of 24	NP_001378885.1	Q70EL1-1
	USP54	NM_001391941.1		c.4411G>A	p.Gly1471Arg	missense	Exon 23 of 24	NP_001378870.1
	USP54	NM_001391953.1		c.4345G>A	p.Gly1449Arg	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.4345G>A	p.Gly1449Arg	missense	Exon 23 of 24	ENSP00000510226.1	Q70EL1-1
	USP54	ENST00000422491.7	TSL:1	c.*1461-1617G>A		intron	N/A	ENSP00000407368.4	A0A804D9U3
	PPP3CB-AS1	ENST00000422977.3	TSL:1	n.1298+1118C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152068 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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000855 AC: 2 AN: 233880 AF XY: 0.0000157

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: 0.0000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000221 AC: 32 AN: 1446280 Hom.: 0 Cov.: 31 AF XY: 0.0000181 AC XY: 13 AN XY: 719684

African (AFR) AF: 0.0000932 AC: 3 AN: 32180

American (AMR) AF: 0.00 AC: 0 AN: 40564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25590

East Asian (EAS) AF: 0.00 AC: 0 AN: 38408

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53248

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5706

European-Non Finnish (NFE) AF: 0.0000199 AC: 22 AN: 1106628

Other (OTH) AF: 0.0000837 AC: 5 AN: 59716

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152068 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74258

African (AFR) AF: 0.0000242 AC: 1 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15274

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000272 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.087
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.86
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.23	N
PhyloP100		0.013
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.14
Sift	Benign	0.52	T
Sift4G	Benign	0.67	T
Polyphen		0.0020	B
Vest4		0.20
MutPred		0.17		Gain of sheet (P = 0.0477)
MVP		0.12
MPC		0.20
ClinPred		0.094	T
GERP RS		-0.97
Varity_R		0.059
gMVP		0.18
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs111294104; hg19: chr10-75260563; COSMIC: COSV60443273; COSMIC: COSV60443273;