rs1165222

Variant names:

• chr1-55172402-G-A
• rs1165222
• NM_015306.3:c.677C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-55172402-G-A
• chr1-55172402-G-C
• chr1-55172402-G-T

Variant summary

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

The NM_015306.3(USP24):​c.677C>T​(p.Thr226Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 1,612,044 control chromosomes in the GnomAD database, including 585,475 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.87 (57083 hom., cov: 31)
  • Exomes 𝑓: 0.85 (528392 hom.)
• Consequence: USP24 NM_015306.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99
• Publications: 41 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=5.2791404E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP24	NM_015306.3	c.677C>T	p.Thr226Ile	missense_variant	Exon 4 of 68	ENST00000294383.7	NP_056121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP24	ENST00000294383.7	c.677C>T	p.Thr226Ile	missense_variant	Exon 4 of 68	5	NM_015306.3	ENSP00000294383.5
USP24	ENST00000484447.6	c.677C>T	p.Thr226Ile	missense_variant	Exon 4 of 68	3		ENSP00000489026.2

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131618 AN: 152074 Hom.: 57038 Cov.: 31

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.878

GnomAD2 exomes AF: 0.877 AC: 217197 AN: 247534 AF XY: 0.875

Gnomad AFR exome AF: 0.866

Gnomad AMR exome AF: 0.929

Gnomad ASJ exome AF: 0.817

Gnomad EAS exome AF: 0.996

Gnomad FIN exome AF: 0.876

Gnomad NFE exome AF: 0.844

Gnomad OTH exome AF: 0.877

GnomAD4 exome AF: 0.850 AC: 1240968 AN: 1459852 Hom.: 528392 Cov.: 45 AF XY: 0.851 AC XY: 618115 AN XY: 726166

African (AFR) AF: 0.869 AC: 29060 AN: 33422

American (AMR) AF: 0.925 AC: 41296 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 21288 AN: 26082

East Asian (EAS) AF: 0.992 AC: 39279 AN: 39606

South Asian (SAS) AF: 0.895 AC: 76990 AN: 86052

European-Finnish (FIN) AF: 0.877 AC: 46769 AN: 53322

Middle Eastern (MID) AF: 0.898 AC: 5168 AN: 5758

European-Non Finnish (NFE) AF: 0.837 AC: 929553 AN: 1110694

Other (OTH) AF: 0.855 AC: 51565 AN: 60294

GnomAD4 genome AF: 0.865 AC: 131721 AN: 152192 Hom.: 57083 Cov.: 31 AF XY: 0.869 AC XY: 64645 AN XY: 74386

African (AFR) AF: 0.863 AC: 35864 AN: 41534

American (AMR) AF: 0.900 AC: 13758 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2845 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5133 AN: 5164

South Asian (SAS) AF: 0.913 AC: 4401 AN: 4822

European-Finnish (FIN) AF: 0.876 AC: 9278 AN: 10594

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.846 AC: 57524 AN: 68004

Other (OTH) AF: 0.879 AC: 1859 AN: 2114

Alfa AF: 0.851 Hom.: 189170

Bravo AF: 0.866

TwinsUK AF: 0.833 AC: 3089

ALSPAC AF: 0.822 AC: 3168

ESP6500AA AF: 0.865 AC: 3176

ESP6500EA AF: 0.844 AC: 6904

ExAC AF: 0.876 AC: 105749

Asia WGS AF: 0.951 AC: 3305 AN: 3474

EpiCase AF: 0.841

EpiControl AF: 0.837

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	15
DANN	Benign	0.74
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	5.3e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N
PhyloP100		3.0
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.47	N
REVEL	Benign	0.054
Sift	Benign	0.67	T
Sift4G	Benign	0.40	T
Vest4		0.031
MPC		0.48
ClinPred		0.0011	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.025
gMVP		0.11
Mutation Taster		=98/2	polymorphism (auto)

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: rs1165222; hg19: chr1-55638075; COSMIC: COSV53764784;