1-55078560-A-T

Position:

• chr1-55078560-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015306.3(USP24):​c.7292T>A​(p.Phe2431Tyr) 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 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: 32)
• Consequence: USP24 NM_015306.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.81

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21732089).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP24	NM_015306.3	c.7292T>A	p.Phe2431Tyr	missense_variant	61/68	ENST00000294383.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP24	ENST00000294383.7	c.7292T>A	p.Phe2431Tyr	missense_variant	61/68	5	NM_015306.3	P1
USP24	ENST00000484447.6	c.7292T>A	p.Phe2431Tyr	missense_variant	61/68	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Mar 22, 2023

The c.7292T>A (p.F2431Y) alteration is located in exon 61 (coding exon 61) of the USP24 gene. This alteration results from a T to A substitution at nucleotide position 7292, causing the phenylalanine (F) at amino acid position 2431 to be replaced by a tyrosine (Y). 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	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Benign	0.78
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.21
Eigen_PC	Benign	0.061
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	0.96	D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.22
Sift	Benign	0.50	T
Sift4G	Uncertain	0.049	D
Vest4		0.50
MVP		0.14
MPC		0.57
ClinPred		0.56	D
GERP RS		5.7
Varity_R		0.12
gMVP		0.18

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: chr1-55544233;