rs367649814

Variant names:

• chr1-55078635-C-A
• NM_015306.3:c.7217G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-55078635-C-A
• chr1-55078635-C-T

Variant summary

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

The NM_015306.3(USP24):​c.7217G>T​(p.Arg2406Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,146 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R2406Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: USP24 NM_015306.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.46

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP24	NM_015306.3	c.7217G>T	p.Arg2406Leu	missense_variant	Exon 61 of 68	ENST00000294383.7	NP_056121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP24	ENST00000294383.7	c.7217G>T	p.Arg2406Leu	missense_variant	Exon 61 of 68	5	NM_015306.3	ENSP00000294383.5
USP24	ENST00000484447.6	c.7217G>T	p.Arg2406Leu	missense_variant	Exon 61 of 68	3		ENSP00000489026.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455146 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723836

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.37
Sift	Benign	0.30	T
Sift4G	Benign	0.20	T
Vest4		0.95
MVP		0.42
MPC		0.81
ClinPred		0.78	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-55544308;