rs12255505

Positions:

• chr10-73529601-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001391956.1(USP54):​c.2060+79G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,522,264 control chromosomes in the GnomAD database, including 15,384 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (4971 hom., cov: 32)
  • Exomes 𝑓: 0.093 (10413 hom.)
• Consequence: USP54 NM_001391956.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP54	NM_001391956.1	c.2060+79G>T		intron_variant		ENST00000687698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP54	ENST00000687698.1	c.2060+79G>T		intron_variant			NM_001391956.1	P3

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28653 AN: 152016 Hom.: 4945 Cov.: 32

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.0448

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0654

Gnomad OTH AF: 0.145

GnomAD3 exomes AF: 0.134 AC: 32832 AN: 245476 Hom.: 3854 AF XY: 0.132 AC XY: 17615 AN XY: 133510

Gnomad AFR exome AF: 0.457

Gnomad AMR exome AF: 0.0984

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.301

Gnomad SAS exome AF: 0.223

Gnomad FIN exome AF: 0.0477

Gnomad NFE exome AF: 0.0659

Gnomad OTH exome AF: 0.0953

GnomAD4 exome AF: 0.0932 AC: 127761 AN: 1370130 Hom.: 10413 Cov.: 23 AF XY: 0.0960 AC XY: 65904 AN XY: 686294

Gnomad4 AFR exome AF: 0.458

Gnomad4 AMR exome AF: 0.0998

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.285

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.0489

Gnomad4 NFE exome AF: 0.0644

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.189 AC: 28734 AN: 152134 Hom.: 4971 Cov.: 32 AF XY: 0.189 AC XY: 14044 AN XY: 74406

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.0448

Gnomad4 NFE AF: 0.0654

Gnomad4 OTH AF: 0.147

Alfa AF: 0.0920 Hom.: 1219

Bravo AF: 0.203

Asia WGS AF: 0.269 AC: 935 AN: 3478

EpiCase AF: 0.0650

EpiControl AF: 0.0644

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.77
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs12255505; hg19: chr10-75289359; COSMIC: COSV60442683; COSMIC: COSV60442683;