Genetic Variant USP24:p.Asn2289Lys (chr1-55083787-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015306.3(USP24):c.6867C>A(p.Asn2289Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

USP24
NM_015306.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48

Variant links:

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]

USP24 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2859934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP24	NM_015306.3 link	c.6867C>A	p.Asn2289Lys	missense_variant	Exon 57 of 68	ENST00000294383.7	NP_056121.2	Q9UPU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
USP24	ENST00000294383.7 link	c.6867C>A	p.Asn2289Lys	missense_variant	Exon 57 of 68	5	NM_015306.3	ENSP00000294383.5	Q9UPU5
USP24	ENST00000484447.6 link	c.6867C>A	p.Asn2289Lys	missense_variant	Exon 57 of 68	3		ENSP00000489026.2	A0A0U1RQI9
USP24	ENST00000472566.1 link	n.585C>A		non_coding_transcript_exon_variant	Exon 2 of 4	3
USP24	ENST00000512504.1 link	n.*56C>A		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1440070

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713980

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.6867C>A (p.N2289K) alteration is located in exon 57 (coding exon 57) of the USP24 gene. This alteration results from a C to A substitution at nucleotide position 6867, causing the asparagine (N) at amino acid position 2289 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

Eigen

Benign

-0.12

Eigen_PC

Benign

0.078

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0053

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.69

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.4

REVEL

Benign

0.094

Sift

Benign

0.13

Sift4G

Uncertain

0.014

Vest4

0.62

MVP

0.082

MPC

0.52

ClinPred

0.65

GERP RS

5.0

Varity_R

0.21

gMVP

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over