chr1-55077293-A-T

Position:

• chr1-55077293-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015306.3(USP24):​c.7322T>A​(p.Leu2441Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: USP24 NM_015306.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.39

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.854

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP24	NM_015306.3	c.7322T>A	p.Leu2441Gln	missense_variant	62/68	ENST00000294383.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP24	ENST00000294383.7	c.7322T>A	p.Leu2441Gln	missense_variant	62/68	5	NM_015306.3	P1
USP24	ENST00000484447.6	c.7322T>A	p.Leu2441Gln	missense_variant	62/68	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000142 AC: 2 AN: 1407914 Hom.: 0 Cov.: 30 AF XY: 0.00000144 AC XY: 1 AN XY: 695880

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: 0.0000400

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.7322T>A (p.L2441Q) alteration is located in exon 62 (coding exon 62) of the USP24 gene. This alteration results from a T to A substitution at nucleotide position 7322, causing the leucine (L) at amino acid position 2441 to be replaced by a glutamine (Q). 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	0.98
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0020	D
Vest4		0.95
MVP		0.64
MPC		1.0
ClinPred		0.98	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.52
gMVP		0.65

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.

Other links and lift over

hg19: chr1-55542966;