rs16930750

Positions:

• chr10-73599700-G-A

Variant summary

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

The NM_001391941.1(USP54):​c.-703-23339C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0511 in 152,072 control chromosomes in the GnomAD database, including 604 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 0.051 (604 hom., cov: 32)
• Consequence: USP54 NM_001391941.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

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]

USP54 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP54	NM_001391941.1	c.-703-23339C>T		intron_variant			NP_001378870.1
USP54	NM_001391953.1	c.-243-23339C>T		intron_variant			NP_001378882.1
USP54	NM_152586.4	c.-17-24025C>T		intron_variant			NP_689799.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP54	ENST00000422491.7	c.-17-24025C>T		intron_variant		1		ENSP00000407368.4
USP54	ENST00000339859.8	c.-17-24025C>T		intron_variant		5		ENSP00000345216.4
USP54	ENST00000689425.1	c.-581-23339C>T		intron_variant				ENSP00000508413.1

Frequencies

GnomAD3 genomes AF: 0.0511 AC: 7762 AN: 151954 Hom.: 601 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0186

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00447

Gnomad OTH AF: 0.0301

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0511 AC: 7776 AN: 152072 Hom.: 604 Cov.: 32 AF XY: 0.0498 AC XY: 3702 AN XY: 74366

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.0186

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00123

Gnomad4 NFE AF: 0.00447

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0329 Hom.: 51

Bravo AF: 0.0575

Asia WGS AF: 0.0110 AC: 39 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.60

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: rs16930750; hg19: chr10-75359458;