rs370609533

Variant names:

• chr1-55081417-C-G
• rs370609533
• NM_015306.3:c.6983G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-55081417-C-G
• chr1-55081417-C-T

Variant summary

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

The NM_015306.3(USP24):​c.6983G>C​(p.Arg2328Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R2328Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: USP24 NM_015306.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.75

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.6983G>C	p.Arg2328Pro	missense_variant	Exon 59 of 68	ENST00000294383.7	NP_056121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP24	ENST00000294383.7	c.6983G>C	p.Arg2328Pro	missense_variant	Exon 59 of 68	5	NM_015306.3	ENSP00000294383.5
USP24	ENST00000484447.6	c.6983G>C	p.Arg2328Pro	missense_variant	Exon 59 of 68	3		ENSP00000489026.2
USP24	ENST00000472566.1	n.701G>C		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248968 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135072

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Vest4		0.81
MVP		0.33
MPC		0.67
ClinPred		0.87	D
GERP RS		6.0
Varity_R		0.37
gMVP		0.71

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

LitVar

Other links and lift over

dbSNP: rs370609533; hg19: chr1-55547090;