1-55172402-G-T

Position:

• chr1-55172402-G-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.677C>A​(p.Thr226Asn) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T226I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: USP24 NM_015306.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99

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 (HGNC:):

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=0.073052496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP24	NM_015306.3	c.677C>A	p.Thr226Asn	missense_variant	4/68	ENST00000294383.7	NP_056121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP24	ENST00000294383.7	c.677C>A	p.Thr226Asn	missense_variant	4/68	5	NM_015306.3	ENSP00000294383.5
USP24	ENST00000484447.6	c.677C>A	p.Thr226Asn	missense_variant	4/68	3		ENSP00000489026.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.042
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.012	D
Vest4		0.24
MVP		0.12
MPC		0.51
ClinPred		0.24	T
GERP RS		2.2
Varity_R		0.10
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1165222; hg19: chr1-55638075;