rs1675662968

Variant names:

• chr1-77714662-C-T
• rs1675662968
• NM_201624.3:c.2167G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_201624.3(USP33):​c.2167G>A​(p.Ala723Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP33 NM_201624.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.68
• Publications: 0 publications found

Genes affected

USP33 (HGNC:20059): (ubiquitin specific peptidase 33) This gene encodes a deubiquinating enzyme important in a variety of processes, including Slit-dependent cell migration and beta-2 adrenergic receptor signaling. The protein is negatively regulated through ubiquitination by von Hippel-Lindau tumor protein (VHL). Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jun 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2247453).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201624.3. 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
	USP33	NM_201624.3	MANE Select	c.2167G>A	p.Ala723Thr	missense	Exon 19 of 24	NP_963918.1	Q8TEY7-2
	USP33	NM_015017.5		c.2260G>A	p.Ala754Thr	missense	Exon 20 of 25	NP_055832.3
	USP33	NM_001377430.1		c.2236G>A	p.Ala746Thr	missense	Exon 20 of 25	NP_001364359.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP33	ENST00000370794.7	TSL:1 MANE Select	c.2167G>A	p.Ala723Thr	missense	Exon 19 of 24	ENSP00000359830.3	Q8TEY7-2
	USP33	ENST00000370793.5	TSL:1	c.2260G>A	p.Ala754Thr	missense	Exon 20 of 25	ENSP00000359829.1	Q8TEY7-1
	USP33	ENST00000370792.7	TSL:1	c.2236G>A	p.Ala746Thr	missense	Exon 20 of 22	ENSP00000359828.3	Q8TEY7-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.0078	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		4.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.19
Sift	Benign	0.039	D
Sift4G	Uncertain	0.056	T
Polyphen		0.79	P
Vest4		0.32
MutPred		0.21		Gain of disorder (P = 0.0963)
MVP		0.43
MPC		1.4
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.39
gMVP		0.70
Mutation Taster		=62/38	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: rs1675662968; hg19: chr1-78180347;