rs775674913

Variant names:

• chr1-55073899-C-A
• rs775674913
• NM_015306.3:c.7455G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-55073899-C-A
• chr1-55073899-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015306.3(USP24):​c.7455G>T​(p.Met2485Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000704 in 1,421,114 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: USP24 NM_015306.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.16
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015306.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP24	NM_015306.3	MANE Select	c.7455G>T	p.Met2485Ile	missense	Exon 64 of 68	NP_056121.2	Q9UPU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP24	ENST00000294383.7	TSL:5 MANE Select	c.7455G>T	p.Met2485Ile	missense	Exon 64 of 68	ENSP00000294383.5	Q9UPU5
	USP24	ENST00000927917.1		c.7452G>T	p.Met2484Ile	missense	Exon 64 of 68	ENSP00000597976.1
	USP24	ENST00000484447.6	TSL:3	c.7455G>T	p.Met2485Ile	missense	Exon 64 of 68	ENSP00000489026.2	A0A0U1RQI9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1421114 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 702578

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32586

American (AMR) AF: 0.00 AC: 0 AN: 38560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25386

East Asian (EAS) AF: 0.00 AC: 0 AN: 37896

South Asian (SAS) AF: 0.00 AC: 0 AN: 80458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 9.17e-7 AC: 1 AN: 1090464

Other (OTH) AF: 0.00 AC: 0 AN: 59040

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	21
DANN	Benign	0.61
DEOGEN2	Benign	0.021	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	-0.045	N
PhyloP100		7.2
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.21	N
REVEL	Uncertain	0.36
Sift	Benign	1.0	T
Sift4G	Uncertain	0.027	D
Vest4		0.68
MVP		0.47
MPC		0.50
ClinPred		0.70	D
GERP RS		5.8
Varity_R		0.22
gMVP		0.40
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

dbSNP: rs775674913; hg19: chr1-55539572;