4-119266456-C-T

Variant names:

• chr4-119266456-C-T
• rs11098499
• NM_001371395.1:c.973-864C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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]

USP53 Gene-Disease associations (from GenCC):

• cholestasis

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics
• cholestasis, progressive familial intrahepatic, 7, with or without hearing loss

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371395.1. 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
	USP53	NM_001371395.1	MANE Select	c.973-864C>T		intron	N/A	NP_001358324.1
	USP53	NM_001371399.1		c.973-864C>T		intron	N/A	NP_001358328.1
	USP53	NM_001389658.1		c.973-864C>T		intron	N/A	NP_001376587.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP53	ENST00000692078.1	MANE Select	c.973-864C>T		intron	N/A	ENSP00000509606.1
	USP53	ENST00000274030.11	TSL:1	c.973-864C>T		intron	N/A	ENSP00000274030.6
	USP53	ENST00000509769.5	TSL:1	n.*22+123C>T		intron	N/A	ENSP00000426628.1

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

African (AFR) AF: 0.222 AC: 1506 AN: 6790

American (AMR) AF: 0.290 AC: 5696 AN: 19668

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 1692 AN: 7940

East Asian (EAS) AF: 0.382 AC: 3292 AN: 8622

South Asian (SAS) AF: 0.172 AC: 8703 AN: 50658

European-Finnish (FIN) AF: 0.268 AC: 2896 AN: 10826

Middle Eastern (MID) AF: 0.205 AC: 331 AN: 1618

European-Non Finnish (NFE) AF: 0.316 AC: 43775 AN: 138396

Other (OTH) AF: 0.277 AC: 3371 AN: 12166

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

African (AFR) AF: 0.220 AC: 9118 AN: 41432

American (AMR) AF: 0.275 AC: 4194 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 730 AN: 3462

East Asian (EAS) AF: 0.384 AC: 1983 AN: 5160

South Asian (SAS) AF: 0.186 AC: 898 AN: 4824

European-Finnish (FIN) AF: 0.266 AC: 2807 AN: 10534

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.323 AC: 21950 AN: 67932

Other (OTH) AF: 0.295 AC: 621 AN: 2106

Alfa AF: 0.304 Hom.: 17539

Bravo AF: 0.286

Asia WGS AF: 0.259 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.57
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs11098499; hg19: chr4-120187611;