4-119266456-C-T

Position:

• chr4-119266456-C-T

Variant summary

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

The NM_001371395.1(USP53):​c.973-864C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 408,598 control chromosomes in the GnomAD database, including 16,668 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 0.28 (6195 hom., cov: 32)
  • Exomes 𝑓: 0.28 (10473 hom.)
• Consequence: USP53 NM_001371395.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143

Genes affected

USP53 (HGNC:29255): (ubiquitin specific peptidase 53) Predicted to enable thiol-dependent deubiquitinase. Predicted to be involved in response to auditory stimulus and sensory perception of sound. Predicted to act upstream of or within action potential and neuron apoptotic process. Predicted to be located in bicellular tight junction. Predicted to be active in cell-cell junction. [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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP53	NM_001371395.1	c.973-864C>T		intron_variant		ENST00000692078.1	NP_001358324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP53	ENST00000692078.1	c.973-864C>T		intron_variant			NM_001371395.1	ENSP00000509606.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42650 AN: 151794 Hom.: 6193 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.278 AC: 71262 AN: 256684 Hom.: 10473 AF XY: 0.266 AC XY: 38816 AN XY: 145720

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.290

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.382

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.268

Gnomad4 NFE exome AF: 0.316

Gnomad4 OTH exome AF: 0.277

GnomAD4 genome AF: 0.281 AC: 42666 AN: 151914 Hom.: 6195 Cov.: 32 AF XY: 0.278 AC XY: 20603 AN XY: 74226

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.295

Alfa AF: 0.312 Hom.: 9345

Bravo AF: 0.286

Asia WGS AF: 0.259 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.57

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: rs11098499; hg19: chr4-120187611;