NM_015306.3:c.7403T>C

Variant names:

• chr1-55075501-A-G
• rs487230
• NM_015306.3:c.7403T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015306.3(USP24):​c.7403T>C​(p.Val2468Ala) variant causes a missense change. The variant allele was found at a frequency of 0.75 in 1,599,694 control chromosomes in the GnomAD database, including 458,963 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (35917 hom., cov: 31)
  • Exomes 𝑓: 0.76 (423046 hom.)
• Consequence: USP24 NM_015306.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.12
• Publications: 46 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.791758E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

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.7403T>C	p.Val2468Ala	missense	Exon 63 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.7403T>C	p.Val2468Ala	missense	Exon 63 of 68	ENSP00000294383.5	Q9UPU5
	USP24	ENST00000927917.1		c.7400T>C	p.Val2467Ala	missense	Exon 63 of 68	ENSP00000597976.1
	USP24	ENST00000484447.6	TSL:3	c.7403T>C	p.Val2468Ala	missense	Exon 63 of 68	ENSP00000489026.2	A0A0U1RQI9

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99565 AN: 151926 Hom.: 35908 Cov.: 31

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.720

GnomAD2 exomes AF: 0.767 AC: 176798 AN: 230382 AF XY: 0.772

Gnomad AFR exome AF: 0.309

Gnomad AMR exome AF: 0.876

Gnomad ASJ exome AF: 0.724

Gnomad EAS exome AF: 0.907

Gnomad FIN exome AF: 0.770

Gnomad NFE exome AF: 0.761

Gnomad OTH exome AF: 0.790

GnomAD4 exome AF: 0.760 AC: 1100278 AN: 1447650 Hom.: 423046 Cov.: 44 AF XY: 0.763 AC XY: 548582 AN XY: 718902

African (AFR) AF: 0.309 AC: 10256 AN: 33204

American (AMR) AF: 0.868 AC: 36815 AN: 42432

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 18685 AN: 25744

East Asian (EAS) AF: 0.901 AC: 35528 AN: 39414

South Asian (SAS) AF: 0.827 AC: 69018 AN: 83414

European-Finnish (FIN) AF: 0.774 AC: 40880 AN: 52816

Middle Eastern (MID) AF: 0.826 AC: 4745 AN: 5742

European-Non Finnish (NFE) AF: 0.760 AC: 839558 AN: 1105008

Other (OTH) AF: 0.748 AC: 44793 AN: 59876

GnomAD4 genome AF: 0.655 AC: 99588 AN: 152044 Hom.: 35917 Cov.: 31 AF XY: 0.663 AC XY: 49313 AN XY: 74324

African (AFR) AF: 0.326 AC: 13525 AN: 41448

American (AMR) AF: 0.814 AC: 12429 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2528 AN: 3472

East Asian (EAS) AF: 0.907 AC: 4698 AN: 5182

South Asian (SAS) AF: 0.844 AC: 4066 AN: 4816

European-Finnish (FIN) AF: 0.769 AC: 8109 AN: 10546

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.761 AC: 51767 AN: 67984

Other (OTH) AF: 0.723 AC: 1527 AN: 2112

Alfa AF: 0.728 Hom.: 162835

Bravo AF: 0.644

TwinsUK AF: 0.763 AC: 2829

ALSPAC AF: 0.750 AC: 2892

ESP6500AA AF: 0.357 AC: 1310

ESP6500EA AF: 0.767 AC: 6284

ExAC AF: 0.750 AC: 90306

Asia WGS AF: 0.840 AC: 2922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	T
MetaRNN	Benign	7.8e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	N
PhyloP100		5.1
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.078
Sift	Benign	0.37	T
Sift4G	Benign	0.35	T
Vest4		0.15
MPC		0.53
ClinPred		0.015	T
GERP RS		4.2
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.023
gMVP		0.21
Mutation Taster		=78/22	polymorphism (auto)

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

Other links and lift over

dbSNP: rs487230; hg19: chr1-55541174; COSMIC: COSV53764127; COSMIC: COSV53764127;