rs593398

Variant names:

• chr1-55076223-T-C
• rs593398
• NM_015306.3:c.7381-700A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000294383.7(USP24):​c.7381-700A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 152,322 control chromosomes in the GnomAD database, including 130 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 0.033 (130 hom., cov: 32)
• Consequence: USP24 ENST00000294383.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• Publications: 0 publications found

Genes affected

USP24 (HGNC:12623): (ubiquitin specific peptidase 24) Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP24 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004 [PubMed 14715245]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000294383.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP24	NM_015306.3	MANE Select	c.7381-700A>G		intron	N/A	NP_056121.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP24	ENST00000294383.7	TSL:5 MANE Select	c.7381-700A>G		intron	N/A	ENSP00000294383.5
	USP24	ENST00000484447.6	TSL:3	c.7381-700A>G		intron	N/A	ENSP00000489026.2

Frequencies

GnomAD3 genomes AF: 0.0329 AC: 5001 AN: 152204 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.00991

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0213

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0302

Gnomad FIN AF: 0.0267

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0534

Gnomad OTH AF: 0.0321

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

GnomAD4 genome AF: 0.0328 AC: 5000 AN: 152322 Hom.: 130 Cov.: 32 AF XY: 0.0306 AC XY: 2276 AN XY: 74486

African (AFR) AF: 0.00986 AC: 410 AN: 41584

American (AMR) AF: 0.0212 AC: 325 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 64 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0301 AC: 145 AN: 4824

European-Finnish (FIN) AF: 0.0267 AC: 283 AN: 10618

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0534 AC: 3634 AN: 68018

Other (OTH) AF: 0.0317 AC: 67 AN: 2112

Alfa AF: 0.0408 Hom.: 54

Bravo AF: 0.0316

Asia WGS AF: 0.0120 AC: 41 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.69
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism

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: rs593398; hg19: chr1-55541896;